by Soli W.

When in evolution did nervous cells evolve? Some current idea

Sponges (Porifera) and Placozoa do not have neurons or nervous systems.

Neurons occurred first in Cindaria (jellyfish, sea anemones, etc.).

The molecular equipment of neurons derived from protein families that were present already much earlier, e.g., in Choanoflagellates.

The evolution of elaborate, fast-signaling nervous systems might have appeared because of predatory behavior that required fast locomotion to obtain food or avoid becoming food. Neurons derived from epithelial cells.

Hypothetical concept:

Before the evolution of neurons (A), specialized epithelial cells detect stimuli and exert effect like movements.

Specific epithelial cells evolved that are specilalized on detecting specific stimuli, e.g. mechanosensory stimuli (B). These cells transmit information onto effector cells, e.g. muscle cells. Please note: the hypothetical sensory neuron like many sensory neurons is a bipolar neuron. Also note the rule: sensory neurons do not innervate each other.

Neurons started synapses with each other (C), and motor neurons have evolved. In the example above schematicing motorneurons from Cnidaria lateral, “tangential” extension (axon collaterals) distribute the information in either direction via reciprocal synapses. This is an exception of the functional polarity rule.

This is a two-layered nervous system, consisting of sensory neurons and motor neurons. The animal can react to a stimulus with a behavioral motor response = Reflex!

The basic plan of the nervous systems of vertebrates is revealed by its development.

The CNS derives from the walls of a water-filled tube. This tube (neural tube) forms during development from ectodermal cells. The process is called “neurulation”.

The tube becomes the ventricular system.

The neural crest forms part of the peripheral nervous system.

Three basic brain vesicles form: prosencephalon (forebrain), mesencephalon (midbrain) and rhombencephalon (hindbrain).

Specialized structures differentiate from the three primary vesicles.

The forebrain differentiates into telencephalon (two vesicles) and diencephalon. Optic vesicles will further differentiate into eyes.

The telencephalon will become to cortical hemipheres, olfactory bulb and the basal ganglia (basal telencephalon). The diencephalon will become the thalamus (“gateway to cortex”) and hypothalamus (control of visceral functions).

The midbrain further differentiates into tectum and tegmentum.

The tectum will differentiate into superior colliculus (receives input from eye) and inferior colliculus (input from ear). The tegmentum will differentiate into substantia nigra and red nucleus (voluntary movements).

The hindbrain further differentiates into medulla and medulla pyramids.

Parts of the hindbrain (rhombencephalon) will differentiate to the cerebellum (“Kleinhirn”)

The rhombencephalon (hindbrain) will differentiate into cerebellum, medulla (e.g., cochlear nuclei) and pons (“switchboard” between cortex and cerebellum). It encompasses the fourth ventricle.

The spinal cord differentiates to form dorsal and ventral horns.

A summary and orientation

What exactly is an ion channel? What is ist molecular composition? How is ion selectivity regulated? Which mechanisms do you know by which the opening/closing probabilty can be regulated?

Ion Channel:

  • Definition: An ion channel is a pore-forming protein that allows the selective passage of ions across cell membranes. It acts as a gate, regulating the flow of ions in and out of cells.

Molecular Composition:

  • Ion channels are typically composed of proteins that span the cell membrane. These proteins consist of multiple subunits, with each subunit contributing to the formation of the channel pore. The subunits may be identical or different, depending on the specific type of ion channel.

Ion Selectivity Regulation:

  • The ion selectivity of an ion channel refers to its ability to allow specific ions to pass while excluding others. This selectivity is primarily determined by the structure of the channel pore, including the arrangement of amino acids within the pore. The size, charge, and coordination properties of the amino acids in the pore determine which ions can pass through.

Regulation of Opening/Closing Probability:

  • Ion channels can be regulated by various mechanisms to control their opening and closing probabilities. Some common mechanisms include:

    1. Voltage-gating: Ion channels can be sensitive to changes in the membrane potential. Voltage-gated channels open or close in response to specific voltage thresholds.

    2. Ligand-gating: Ion channels can be activated or inhibited by the binding of specific molecules, such as neurotransmitters or hormones. Ligand-gated channels open or close upon binding of the ligand.

    3. Phosphorylation: The addition or removal of phosphate groups can modulate the activity of ion channels. Phosphorylation by protein kinases can lead to channel opening or closing, while dephosphorylation can have the opposite effect.

    4. Temperature: Temperature changes can affect the opening and closing probabilities of some ion channels. Cold temperatures may cause channels to close, while heat can lead to channel opening.

    5. Mechanical stress: Certain ion channels are sensitive to mechanical forces. Physical pressure or stretch can influence their opening and closing.

Calculate the equilibrium potential for calcium, sodium, potassium and chloride!

Equilibrium Potentials:

1. Calcium (Ca2+):

- Assuming typical concentrations:

- Extracellular concentration: 1.5 mM

- Intracellular concentration: 0.1 μM (0.1 x 10^-3 mM)

- Using the Nernst equation:

E_Ca2+ = (RT/zF) * ln([Ca2+]outside/[Ca2+]inside)

- R: Gas constant (8.314 J/(mol·K))

- T: Absolute temperature (usually around 298 K)

- z: Valence of the ion (charge), which is 2 for calcium

- F: Faraday's constant (96,485 C/mol)

Plugging in the values:

E_Ca2+ = (8.314 * 298 / (2 * 96,485)) * ln(1.5 / 0.1 x 10^-3)

The equilibrium potential for calcium (Ca2+) is approximately +123 mV.

2. Sodium (Na+):

- Assuming typical concentrations:

- Extracellular concentration: 145 mM

- Intracellular concentration: 15 mM

- Using the Nernst equation:

E_Na+ = (RT/zF) * ln([Na+]outside/[Na+]inside)

- z: Valence of the ion, which is 1 for sodium

Plugging in the values:

E_Na+ = (8.314 * 298 / (1 * 96,485)) * ln(145 / 15)

The equilibrium potential for sodium (Na+) is approximately +61 mV.

3. Potassium (K+):

- Assuming typical concentrations:

- Extracellular concentration: 5 mM

- Intracellular concentration: 140 mM

- Using the Nernst equation:

E_K+ = (RT/zF) * ln([K+]outside/[K+]inside)

- z: Valence of the ion, which is 1 for potassium

Plugging in the values:

E_K+ = (8.314 * 298 / (1 * 96,485)) * ln(5 / 140)

The equilibrium potential for potassium (K+) is approximately -94 mV.

4. Chloride (Cl-):

- Assuming typical concentrations:

- Extracellular concentration: 105 mM

- Intracellular concentration: 10 mM

- Using the Nernst equation:

E_Cl- = (RT/zF) * ln([Cl-]outside/[Cl-]inside)

- z: Valence of the ion, which is -1 for chloride

Plugging in the values:

E_Cl- = (8.314 * 298 / (-1 * 96,485)) * ln(105 / 10)

The equilibrium potential for chloride (Cl-) is approximately -62 mV.

Note: These values are approximate and can vary depending on the actual concentrations used and the temperature conditions.

What happens if sodium, potassium, chloride or calcium channels are opened in

the membrane of a neuron that is at a resting potential of -70mV?

Effect of Ion Channel Opening at Resting Potential (-70mV) in a Neuron:

  1. Sodium (Na+) Channels:

  • Opening of Na+ channels at resting potential results in an influx of Na+ ions into the neuron.

  • Since the equilibrium potential for Na+ is around +61 mV, which is more positive than the resting potential (-70 mV), Na+ ions move into the cell.

  • This influx of positive charges depolarizes the neuron, making the membrane potential less negative or even positive.

  • If the depolarization reaches the threshold potential (around -55 mV to -50 mV), it can trigger an action potential, leading to the propagation of an electrical signal along the neuron.

  1. Potassium (K+) Channels:

  • Opening of K+ channels at resting potential allows K+ ions to move out of the neuron.

  • The equilibrium potential for K+ is around -94 mV, which is more negative than the resting potential.

  • As K+ ions move out of the cell, it contributes to hyperpolarization, making the membrane potential more negative.

  • This hyperpolarization makes it more difficult to reach the threshold potential, reducing the excitability of the neuron.

  1. Chloride (Cl-) Channels:

  • Opening of Cl- channels at resting potential allows Cl- ions to move according to their concentration gradient.

  • The equilibrium potential for Cl- is around -61 mV, which is close to the resting potential.

  • Opening Cl- channels does not cause significant changes in the membrane potential unless there are other ionic imbalances or active transport mechanisms involved.

  1. Calcium (Ca2+) Channels:

  • Opening of Ca2+ channels at resting potential allows Ca2+ ions to enter the neuron.

  • The equilibrium potential for Ca2+ is around +123 mV, which is much more positive than the resting potential.

  • Influx of Ca2+ ions can have various effects depending on the specific neuron and its signaling pathways.

  • Ca2+ ions play a crucial role in neuronal functions, including neurotransmitter release and intracellular signaling processes.

Note: The specific effects of ion channel opening may vary depending on the neuronal context, ion channel subtype, and other factors.

What is an electrogenic pump? What is the sodium-potassium-ATPase good for

in neurons?

Electrogenic Pump:


An electrogenic pump is a type of ion pump that actively transports ions across the cell membrane, contributing to the generation or maintenance of the membrane potential. It creates an electrogenic effect, meaning it generates a net charge separation across the membrane.


  • The sodium-potassium-ATPase, also known as the Na+/K+ pump, is an example of an electrogenic pump found in neurons.

Function in Neurons:

  • The primary role of the sodium-potassium-ATPase in neurons is to maintain the resting membrane potential and regulate the ionic balance inside and outside the cell.

  • It actively transports three sodium ions (Na+) out of the neuron for every two potassium ions (K+) it brings in, using energy from ATP hydrolysis.

  • This process helps establish and maintain the concentration gradients of sodium and potassium ions, which are essential for generating and propagating electrical signals in neurons.

  • By pumping out sodium ions and bringing in potassium ions, the sodium-potassium-ATPase contributes to the negative resting membrane potential (-70 mV) of neurons.

  • Furthermore, it plays a critical role in restoring the ion concentrations after the action potential, helping to reset the neuron for subsequent signaling events.

Note: The sodium-potassium-ATPase is a fundamental component of neuronal function, ensuring the proper excitability and signaling capabilities of neurons.

What is the effect of lidocaine, tetrodotoxin and tetraethylammonium?

  1. Lidocaine:

  • Lidocaine is a local anesthetic that blocks voltage-gated sodium channels.

  • It inhibits the propagation of action potentials by preventing the opening of sodium channels.

  • As a result, lidocaine reduces the excitability of neurons and blocks the transmission of pain signals.

  1. Tetrodotoxin:

  • Tetrodotoxin is a potent neurotoxin found in certain marine organisms, such as pufferfish.

  • It selectively blocks voltage-gated sodium channels, specifically the pore region.

  • By binding to the sodium channels, tetrodotoxin prevents the influx of sodium ions during an action potential.

  • This leads to the inhibition of nerve impulse transmission, causing paralysis and potential respiratory failure.

  1. Tetraethylammonium:

  • Tetraethylammonium (TEA) is a potassium channel blocker.

  • It inhibits voltage-gated potassium channels, specifically delaying their repolarizing effect during an action potential.

  • By blocking potassium channels, TEA prolongs the duration of the action potential and increases neuronal excitability.

  • It can affect the firing frequency and pattern of action potentials in neurons.

Note: These substances have specific effects on ion channels, altering the normal electrical activity of neurons. Lidocaine and tetrodotoxin target sodium channels, while tetraethylammonium affects potassium channels. Understanding the actions of these compounds is essential in studying neuronal function and developing treatments for various conditions.

Depolarization of a membrane to +20mV causes sodium influx, depolarization to

+80mV sodium eflux. Why?

Depolarization to +20mV causes sodium influx, while depolarization to +80mV causes sodium efflux due to the voltage-gated nature of sodium channels.


Voltage-gated sodium channels are responsible for the flow of sodium ions across the cell membrane. These channels have different conformational states depending on the membrane potential.

  1. Depolarization to +20mV:

    • At +20mV, which is above the threshold potential, voltage-gated sodium channels undergo a conformational change and transition from a closed state to an open state.

    • This conformational change occurs as a response to the depolarization of the membrane.

    • Opening of the sodium channels allows sodium ions to flow into the cell, resulting in sodium influx.

    • The influx of positive sodium ions further depolarizes the membrane, contributing to the initiation and propagation of an action potential.

  1. Depolarization to +80mV:

    • At +80mV, which is a highly positive membrane potential, the voltage-gated sodium channels are inactivated.

    • Inactivation occurs as a result of sustained depolarization, causing the inactivation gate to close and block the ion pathway.

    • In the inactivated state, the sodium channels are refractory to further depolarization and cannot open.

    • As a result, depolarization to +80mV does not allow sodium influx, and instead, sodium efflux is observed.

The voltage-dependent behavior of sodium channels enables them to respond to changes in membrane potential and regulate the flow of sodium ions accordingly. Depolarization to +20mV opens the channels, allowing sodium influx, while depolarization to +80mV results in channel inactivation, preventing further sodium influx and leading to sodium efflux.

How are graded memebrane potential changes generated?

Graded membrane potential changes are generated through the activation of ligand-gated or mechanically-gated ion channels in response to specific stimuli. When these channels are opened, they allow the selective movement of ions across the cell membrane, resulting in a change in the membrane potential.

Ligand-gated ion channels are proteins that have binding sites for specific molecules called ligands, which can be neurotransmitters, hormones, or other signaling molecules. When a ligand binds to the channel, it induces a conformational change, leading to the opening of the channel. This allows ions to flow through the channel, either into or out of the cell, based on the specific characteristics of the channel. The movement of ions creates a local change in the membrane potential, which can be either depolarization (becoming less negative) or hyperpolarization (becoming more negative).

Mechanically-gated ion channels, on the other hand, respond to physical forces applied to the cell membrane. These forces can include pressure, stretch, or vibration. When the membrane is mechanically deformed, the ion channels embedded within it open or close, allowing ions to move across the membrane and changing the membrane potential.

The magnitude of the graded membrane potential change depends on the strength or intensity of the stimulus. A stronger stimulus leads to a larger opening of ion channels and a greater ion flow, resulting in a more significant change in membrane potential. Graded potentials allow cells to generate diverse and adaptable responses to various stimuli, playing a crucial role in sensory perception, neuronal communication, and other physiological processes.

  1. Gradedmembranepotentialchanges:

    • incoming short-distance signals;

    • short-lived and localized;

    • depolarizations and hyperpolarizations are possible;

    • Graded membrane potentials spread along the neurites as local currents change adjacent regions of the membrane!

Please explain the terms “time constant” and “length constant” and how these parameters depend on electrical properties of the neuronal membranes (formulas!).

Time constant:

The time constant (τ) of a neuronal membrane refers to the time it takes for the membrane potential to reach approximately 63.2% of its final value during the charging or discharging process. It is determined by the product of the membrane resistance (Rm) and the membrane capacitance (Cm).

The formula for the time constant is τ = Rm * Cm.

Length constant:

The length constant (λ) represents the distance over which a graded potential propagates along the neuronal membrane without significant decay. It depends on the membrane resistance (Rm) and the axial resistance (Ra) of the neuronal processes (such as dendrites or axons).

The formula for the length constant is λ = √(Rm / (2 * Ra)).

The time constant and length constant are influenced by the electrical properties of the neuronal membranes.

The membrane resistance (Rm) determines how easily ions can flow through the membrane

The membrane capacitance (Cm) relates to the ability of the membrane to store electrical charge.

The axial resistance (Ra) represents the resistance to ion flow within the neuronal processes.

Overall, these parameters play crucial roles in the integration and transmission of electrical signals in neurons. The time constant affects the speed of charging or discharging of the membrane, while the length constant determines the extent of signal propagation without significant attenuation.

What is meant by the terms vesicle docking, priming and fusion?

Vesicle docking:

Vesicle docking is the initial step in membrane fusion, where a vesicle approaches the target membrane and aligns in close proximity to it. Specific interactions between proteins on the vesicle membrane (v-SNAREs) and proteins on the target membrane (t-SNAREs) contribute to the docking process. This brings the vesicle into a position ready for further fusion events.

Vesicle priming:

After docking, vesicle priming occurs, which involves a series of molecular events that prepare the vesicle for fusion. During priming, the vesicle undergoes changes in protein composition and structural rearrangements, ensuring that it is in a "primed" state and ready for fusion. This process involves the recruitment of additional proteins and the buildup of calcium ions, which play a crucial role in triggering the subsequent fusion event.

Vesicle fusion:

Vesicle fusion is the final step in the process, where the vesicle and target membrane merge together, allowing the contents of the vesicle to be released into the target compartment. The SNARE proteins on the vesicle (v-SNAREs) and target (t-SNAREs) membranes interact and form a stable SNARE complex, which catalyzes the fusion process. The fusion event involves the merging of lipid bilayers, resulting in the complete integration of the vesicle membrane with the target membrane.

Together, vesicle docking, priming, and fusion constitute the sequential stages of the membrane fusion process, ensuring precise and controlled release of vesicle contents into the target membrane.

Please explain in your own words how synaptic vesicles are recycled (steps of the synaptic vesicle cycle).

key steps of the synaptic vesicle cycle:

  1. Neurotransmitter Release: Upon stimulation, synaptic vesicles fuse with the presynaptic membrane, leading to the release of neurotransmitters into the synaptic cleft.

  2. Endocytosis: After neurotransmitter release, the empty vesicle membrane is retrieved from the presynaptic membrane through endocytosis. Clathrin-coated pits form around the vesicle, internalizing it to form an endocytic vesicle.

  3. Uncoating: The clathrin coat is shed from the endocytic vesicle, which then becomes an uncoated endocytic vesicle.

  4. Vesicle Refilling: The uncoated endocytic vesicle undergoes a process called vesicle refilling. Neurotransmitters are replenished within the vesicle by specific transporters, which actively import neurotransmitter molecules from the cytoplasm into the vesicle.

  5. Vesicle Maturation: The refilled vesicle matures and acquires a new coat of clathrin, becoming a recycling vesicle.

  6. Vesicle Re-Primed: The recycling vesicle is re-primed to become ready for subsequent rounds of exocytosis. This step involves the reloading of calcium ions and the reformation of the SNARE complex, preparing the vesicle for fusion with the presynaptic membrane.

  7. Vesicle Exocytosis: Upon the arrival of a new action potential, the re-primed recycling vesicle fuses with the presynaptic membrane, leading to the release of neurotransmitters and the completion of the synaptic vesicle cycle.

In summary, the synaptic vesicle cycle involves the release of neurotransmitters, followed by endocytosis, vesicle refilling, maturation, re-priming, and subsequent exocytosis. This recycling process ensures the continuous availability of synaptic vesicles and efficient neurotransmitter release at synapses.

Name 10 different transmitter substances, their molecular classes and whether they typically act as excitatory or inhibitory tranbsmitter.

  1. Acetylcholine

    • Molecular Class: Biogenic amine/ cholinergics

    • Excitatory or Inhibitory: Can act as both excitatory and inhibitory depending on the receptor subtype and location in the nervous system.

  2. Glutamate

    • Molecular Class: Amino acid

    • Excitatory or Inhibitory: Excitatory. It is the primary excitatory neurotransmitter in the central nervous system.

  3. GABA (gamma-aminobutyric acid)

    • Molecular Class: Amino acid

    • Excitatory or Inhibitory: Inhibitory. It is the primary inhibitory neurotransmitter in the central nervous system.

  4. Dopamine

    • Molecular Class: Biogenic amine/ phenethylamines and derivates

    • Excitatory or Inhibitory: Can act as both excitatory and inhibitory depending on the receptor subtype and brain region.

  5. Serotonin

    • Molecular Class: Biogenic amine/ indoleamines

    • Excitatory or Inhibitory: Can act as both excitatory and inhibitory depending on the receptor subtype and brain region.

  6. Noradrenaline (norepinephrine)

    • Molecular Class: Biogenic amine/ phenethylamines and derivates

    • Excitatory or Inhibitory: Can act as both excitatory and inhibitory depending on the receptor subtype and brain region.

  7. Histamine

    • Molecular Class: amino acids

    • Excitatory or Inhibitory: Can act as both excitatory and inhibitory depending on the receptor subtype and brain region.

  8. Glycine

    • Molecular Class: Amino acid

    • Excitatory or Inhibitory: Inhibitory. It serves as an inhibitory neurotransmitter in the spinal cord and brainstem.

  9. Adenosine

    • Molecular Class: Purine nucleoside

    • Excitatory or Inhibitory: Inhibitory. It acts as an inhibitory neuromodulator in the central nervous system.

  10. Substance P

    • Molecular Class: Neuropeptide

    • Excitatory or Inhibitory: Generally considered excitatory. It is involved in pain transmission and neurogenic inflammation.

Please describe the neuronal pathway underlying the shadow reflex in Barnacles. Which cells are involved, what are their physiological properties and why is there an inverting cell in the circuit?

The shadow reflex in barnacles involves a neuronal pathway that allows the organism to respond to changes in light intensity and adjust its position to remain in darker areas.

1. Photoreceptor Cells: Barnacles have specialized photoreceptor cells located in their eyestalks that detect changes in light intensity. These cells are sensitive to light and generate electrical signals in response to light stimulation.

2. Photoreceptor Output Neurons: The electrical signals from the photoreceptor cells are transmitted to a group of output neurons. These output neurons receive inputs from multiple photoreceptor cells and integrate the information.

3. Excitatory Projection Neurons: The output neurons then send excitatory signals to the motor neurons responsible for muscle contractions. These excitatory projection neurons transmit signals that promote muscle contraction, leading to the extension of the barnacle's body.

4. Inhibitory Interneuron: An inhibitory interneuron is present in the pathway between the output neurons and motor neurons. This interneuron receives excitatory input from the output neurons but has an inhibitory effect on the motor neurons.

5. Inverting Cell: The inhibitory interneuron is connected to an inverting cell, which, instead of inhibiting the motor neurons, activates them. The inverting cell acts as a switch, converting the inhibitory signal from the inhibitory interneuron into an excitatory signal for the motor neurons.

The physiological properties of the involved cells vary. The photoreceptor cells are specialized for light detection, converting light stimuli into electrical signals. The output neurons integrate signals from multiple photoreceptor cells and transmit excitatory information. The inhibitory interneuron receives excitatory inputs from the output neurons and provides inhibitory input to the motor neurons. Finally, the inverting cell receives inhibitory input from the inhibitory interneuron but outputs excitatory signals to the motor neurons.

The presence of an inverting cell in the circuit is crucial for the shadow reflex pathway. It allows the inhibitory signal from the inhibitory interneuron to be converted into an excitatory signal, effectively activating the motor neurons and promoting the appropriate response of muscle contraction for repositioning the barnacle in darker areas. The inverting cell ensures the proper directionality and coordination of the shadow reflex response.

How does the protein kinase A act to modulate synaptic vesicle release in Aplysia?

  1. Activation of PKA: The activation of PKA is triggered by an increase in intracellular levels of cyclic adenosine monophosphate (cAMP). This can occur when a neurotransmitter, such as serotonin, binds to its receptor on the presynaptic membrane, leading to the activation of adenylyl cyclase, an enzyme that synthesizes cAMP.

  2. PKA Translocation: Once activated, PKA translocates from the cytoplasm to various target sites within the presynaptic terminal. This translocation is facilitated by the binding of cAMP to the regulatory subunits of PKA, releasing the catalytic subunits that are responsible for the downstream signaling.

  3. Phosphorylation of Proteins: The catalytic subunits of PKA phosphorylate a variety of proteins within the presynaptic terminal. One key target of PKA phosphorylation is the voltage-gated calcium channels (VGCCs) that mediate calcium entry into the presynaptic terminal upon depolarization. Phosphorylation of VGCCs by PKA increases their activity, leading to an enhanced influx of calcium ions.

  4. Calcium-Dependent Events: The increased calcium influx resulting from PKA-mediated phosphorylation of VGCCs triggers several downstream events. This includes the activation of protein kinases and the modulation of proteins involved in neurotransmitter release, such as synaptotagmin and synapsin.

  5. Enhanced Synaptic Vesicle Release: The cumulative effects of PKA-mediated phosphorylation events ultimately lead to an enhancement of synaptic vesicle release. These include an increase in the probability of vesicle fusion with the presynaptic membrane and alterations in the readily releasable pool of vesicles available for release.

By modulating the activity of presynaptic proteins involved in calcium entry and neurotransmitter release, PKA regulates the strength of synaptic transmission in Aplysia. This PKA-mediated modulation of synaptic vesicle release contributes to the plasticity of synaptic connections and the cellular mechanisms underlying learning and memory in the animal.

Please explain the intracellular signaling cascades underlying sensitization of the gill withdrawal reflex in Aplysia!

  1. Serotonin Release: Sensitization is often induced by the release of serotonin, which acts as a modulatory neurotransmitter. Serotonin is released by a facilitating interneuron onto the sensory neuron responsible for the gill withdrawal reflex.

  2. Activation of Serotonin Receptors: Serotonin binds to specific receptors on the sensory neuron, initiating intracellular signaling cascades. In Aplysia, the most well-known receptor involved is the serotonin receptor 5-HT2A.

  3. Activation of Adenylyl Cyclase: Activation of the serotonin receptor leads to the activation of adenylyl cyclase, an enzyme that synthesizes cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP).

  4. Activation of Protein Kinase A (PKA): Increased cAMP levels result in the activation of protein kinase A (PKA), a key intracellular signaling molecule. PKA translocates from the cytoplasm to various target sites within the sensory neuron.

  5. Phosphorylation of Proteins: Once activated, PKA phosphorylates various proteins involved in the regulation of synaptic strength. This includes the phosphorylation of ion channels, such as potassium channels, which results in their decreased activity and prolonged membrane depolarization.

  6. Modulation of Calcium Channels: PKA phosphorylation also modulates voltage-gated calcium channels (VGCCs) in the presynaptic terminal of the sensory neuron. This enhances calcium influx upon action potential initiation, leading to increased calcium-dependent processes.

  7. Enhanced Neurotransmitter Release: The increased calcium influx triggers enhanced neurotransmitter release from the sensory neuron onto the motor neuron involved in the gill withdrawal reflex. This results in an amplified response and sensitization of the reflex.

What does the term “long-term potentiation” mean? Name some properties of this type of sybaptic plasticity.

Long-term potentiation (LTP) is a form of synaptic plasticity that refers to a long-lasting strengthening of the synaptic connection between two neurons. It is considered a cellular mechanism underlying learning and memory formation in the brain.

Some properties of this type of long-term potentiation:

  1. Cooperativity: LTP can be induced by cooperative activation of presynaptic and postsynaptic neurons. When the presynaptic neuron repeatedly and persistently fires while the postsynaptic neuron is depolarized, LTP can be triggered. Enough afferent fibers must be activated.

  2. Input specificity: LTP exhibits input specificity, meaning it is specific to the synapses that were activated during the induction process. Only the synapses that experienced a high level of activity or stimulation undergo potentiation, while neighboring synapses remain unaffected. Only those synapses are potentiated whose pre- and postsynaptic cells are coincidently active.

  3. Associativity: LTP can display associativity, meaning that weakly stimulated synapses that are coincidently activated alongside strongly stimulated synapses can also undergo potentiation. This property allows for the associative linking of different inputs and strengthens their connections. Weakly activated synapses (sub- threshold) if the postsynaptic cell is coincidently activated by a different, strong input.

  4. Synaptic Strength Enhancement: LTP results in an increase in the strength of synaptic transmission. It leads to a more robust and efficient communication between the presynaptic and postsynaptic neurons.

  5. Persistent Changes: LTP is characterized by its long-lasting effects. Once induced, it can persist for an extended period, ranging from hours to days or even longer. This sustained enhancement of synaptic strength is thought to contribute to the long-term storage of information.

  6. Involvement of NMDA Receptors: NMDA receptors play a crucial role in the induction of LTP. These receptors are a subtype of glutamate receptors and require both presynaptic glutamate release and postsynaptic depolarization for activation. The influx of calcium through NMDA receptors triggers various intracellular signaling pathways that lead to the potentiation of the synapse.

  7. Role in Learning and Memory: LTP is believed to be one of the key cellular mechanisms underlying learning and memory formation. The persistent strengthening of synaptic connections through LTP is thought to contribute to the encoding and storage of new information.

Overall, long-term potentiation is a process of enduring synaptic enhancement that is input-specific, associative, and critically involved in learning and memory. It involves the activation of specific receptors and intracellular signaling pathways, leading to persistent changes in synaptic strength.

What are the roles of the two types of glutamate receptors, the AMPA receptor and the NMDA receptor, for long-term potentiation?

  1. AMPA Receptor:

    • Role in Baseline Transmission: AMPA receptors mediate the majority of fast excitatory synaptic transmission in the central nervous system under normal conditions.

    • Initial Synaptic Response: When glutamate is released from the presynaptic neuron, it binds to and activates the AMPA receptors on the postsynaptic membrane. Activation of AMPA receptors allows the influx of sodium ions, resulting in a rapid depolarization of the postsynaptic membrane and the generation of excitatory postsynaptic potentials (EPSPs).

    • Contribution to LTP Induction: During the early phase of LTP induction, the activation of AMPA receptors is critical. The influx of sodium ions through AMPA receptors leads to depolarization and the removal of a voltage-dependent magnesium block at NMDA receptors, allowing them to be activated.

  2. NMDA Receptor:

    • Requirement for LTP Induction: NMDA receptors play a crucial role in the induction of LTP. They are voltage-dependent and require both presynaptic glutamate release and postsynaptic depolarization to become activated.

    • Coincidence Detection: NMDA receptors are involved in coincidence detection. They require the presynaptic release of glutamate and the postsynaptic depolarization, which relieves the magnesium block, allowing calcium ions to enter the postsynaptic neuron. Calcium influx through NMDA receptors triggers various intracellular signaling pathways that lead to the long-lasting changes associated with LTP.

    • Synaptic Plasticity: Once NMDA receptors are activated, the calcium ions that enter the postsynaptic neuron initiate various intracellular processes, including the activation of protein kinases and the synthesis of new proteins. These processes contribute to the strengthening and potentiation of the synaptic connection, leading to long-term changes in synaptic efficacy.

In summary, the AMPA receptor is responsible for the initial synaptic response and depolarization, while the NMDA receptor plays a pivotal role in coincidence detection and the induction of LTP. The activation of NMDA receptors triggers calcium-dependent signaling cascades that lead to the molecular and cellular changes underlying the long-lasting synaptic potentiation observed in LTP.

Please explain how a network of distributed synapses can store a neuronal pattern as a “memory”.

A network of distributed synapses can store a neuronal pattern as a "memory" through a process known as synaptic plasticity and the concept of Hebbian learn

  1. Synaptic Connections: In a neural network, individual neurons are connected to each other through synapses, which are the points of communication between neurons. Each synapse consists of a presynaptic terminal from one neuron and a postsynaptic terminal on another neuron.

  2. Hebbian Learning: Hebbian learning is a fundamental principle that states "neurons that fire together, wire together." It suggests that when two connected neurons are repeatedly activated in close temporal proximity, the synaptic connection between them is strengthened. This synaptic strengthening occurs through a process called long-term potentiation (LTP).

  3. Long-Term Potentiation (LTP): LTP is a form of synaptic plasticity that leads to the long-lasting enhancement of synaptic strength. When a presynaptic neuron repeatedly activates a postsynaptic neuron, it triggers a series of intracellular signaling events. This signaling cascade involves the activation of various proteins and the strengthening of the synaptic connection. As a result, the postsynaptic neuron becomes more responsive to the signals from the presynaptic neuron.

  4. Distributed Synaptic Connections: In a network of interconnected neurons, a specific pattern of activation across multiple synapses can represent a particular memory or information. The pattern is encoded by the specific pattern of synaptic connections and their strengths within the network.

  5. Pattern Recognition and Retrieval: When a partial cue or input activates a subset of neurons within the network, the distributed synaptic connections allow for pattern completion and retrieval of the complete memory or information associated with that pattern. The activated subset of neurons triggers the reactivation of the entire pattern through interconnected synaptic connections, allowing for pattern recognition and retrieval.

By adjusting the strengths of synaptic connections and establishing specific patterns of activation, a network of distributed synapses can store and retrieve neuronal patterns as memories. This distributed and interconnected nature of synapses provides flexibility, resilience, and capacity for information storage and retrieval in the brain.

Can you spot molecular similarities between the synaptic plasticity found in Aplysia and LTP in the hippocampus? Which molecules are similar?

Yes, there are molecular similarities between synaptic plasticity in Aplysia and long-term potentiation (LTP) in the hippocampus. While there are specific differences due to the distinct characteristics of these systems, some key molecules play similar roles in both forms of synaptic plasticity.

  1. NMDA Receptors: NMDA receptors have a central role in both Aplysia and hippocampal LTP. Activation of NMDA receptors is critical for the induction of LTP in the hippocampus, as well as for the induction of sensitization in Aplysia. NMDA receptors contribute to calcium influx, which triggers intracellular signaling cascades that lead to synaptic plasticity.

  2. Calcium Signaling: Calcium ions serve as a crucial signaling molecule in both Aplysia and hippocampal LTP. Calcium influx through NMDA receptors in the hippocampus and other calcium channels in Aplysia is involved in the activation of various downstream signaling pathways that regulate synaptic plasticity.

  3. Protein Kinase A (PKA): PKA is a key signaling molecule that plays a role in both Aplysia and hippocampal LTP. In Aplysia, PKA is involved in the modulation of synaptic strength and is required for the expression of long-term facilitation. In the hippocampus, PKA activation is also implicated in the induction and expression of LTP.

  4. Protein Kinase C (PKC): PKC is another protein kinase that is involved in both Aplysia and hippocampal LTP. It is an important modulator of synaptic plasticity and is activated during the induction and expression of both forms of plasticity.

  5. CREB (cAMP Response Element-Binding Protein): CREB is a transcription factor that plays a role in both Aplysia and hippocampal LTP. It is involved in the long-lasting changes associated with synaptic plasticity and is implicated in the regulation of gene expression necessary for long-term changes in synaptic strength.

While there are also differences in molecular mechanisms and specific signaling pathways between Aplysia and hippocampal LTP, these shared molecular components highlight some common underlying principles of synaptic plasticity across different model systems.

Please define the terms “Zeitgeber”, circadian rhythm, entrainment and free running cycle.

  • Zeitgeber: Zeitgeber refers to an external cue or stimulus that helps regulate and synchronize an organism's internal biological rhythms with the external environment. It serves as a "time giver" that helps set or entrain the biological clock.

  • Circadian Rhythm: Circadian rhythm refers to a roughly 24-hour cycle that influences various physiological and behavioral processes in organisms. It regulates the sleep-wake cycle, hormone production, body temperature, and other biological functions. Circadian rhythms are driven by an internal biological clock and can be influenced by zeitgebers such as light, temperature, and social cues.

  • Entrainment: Entrainment is the process by which an organism's internal biological rhythms, such as the circadian rhythm, align and synchronize with external cues or zeitgebers. It involves adjusting the timing and phase of the internal clock in response to environmental cues, ensuring that the biological rhythms stay in harmony with the external world.

  • Free Running Cycle: The free running cycle refers to the natural rhythm of an organism's internal clock when it is isolated from external cues or zeitgebers. In the absence of external time cues, an organism's internal biological rhythm will continue to cycle, but it may not align precisely with the 24-hour day. The duration of the free running cycle may be slightly longer or shorter than 24 hours, indicating the intrinsic period of the internal clock.

Please describe the cellular principle of an internal clock by explaining the function of the timeless and period genes in Drosophila. How do they generate a rhythm?

In Drosophila (fruit flies), the timeless (tim) and period (per) genes play a crucial role in generating a rhythm through a cellular principle known as transcription-translation feedback loop. Here's an overview of how these genes function and contribute to the generation of a rhythm:

  1. Transcription: In the morning, the CLOCK-CYCLE (CLK-CYC) protein complex binds to specific DNA regions called E-boxes in the promoter region of the per and tim genes. This binding leads to the activation of gene transcription.

  2. Translation: The newly transcribed mRNA molecules of per and tim are then processed and translated into PER and TIM proteins.

  3. Protein Accumulation: As the day progresses, the PER and TIM proteins accumulate within the cytoplasm of the cells.

  4. Nuclear Entry: Eventually, the PER and TIM proteins form a complex and enter the cell nucleus.

  5. Inhibition of Transcription: Once in the nucleus, the PER-TIM complex inhibits the activity of the CLK-CYC complex, preventing further transcription of per and tim genes.

  6. Degradation: Over time, the PER and TIM proteins undergo degradation, reducing their levels in the cytoplasm.

  7. Relief of Transcription Inhibition: As the PER and TIM protein levels decrease, their inhibition on CLK-CYC is alleviated, allowing the transcription of per and tim genes to resume.

  8. Cycle Restart: The newly transcribed per and tim mRNA molecules are again translated into PER and TIM proteins, initiating a new cycle of accumulation, nuclear entry, inhibition, degradation, and relief.

This transcription-translation feedback loop between the PER-TIM complex and the CLK-CYC complex creates a rhythmic pattern of protein accumulation and degradation, leading to oscillations in gene expression levels. The time it takes for the PER and TIM proteins to accumulate, inhibit transcription, degrade, and relieve inhibition determines the duration of the cycle, resulting in a roughly 24-hour rhythm.

The timely and coordinated interactions between the per and tim genes and their protein products enable the generation of a cellular clock that drives the circadian rhythm in Drosophila. This principle of transcription-translation feedback loops is found in various organisms and plays a fundamental role in regulating circadian rhythms across species, including humans.

Where in the mammalian brain is the “master clock” located and how does it receive optical Zeitgeber input?

The "master clock" in mammals is located in an area of the brain called the suprachiasmatic nucleus (SCN). The SCN is a small, paired structure located in the hypothalamus, specifically above the optic chiasm, which is where the optic nerves cross.

The SCN receives optical zeitgeber input primarily through a specialized population of retinal ganglion cells called intrinsically photosensitive retinal ganglion cells (ipRGCs). These cells contain a photopigment called melanopsin, which is sensitive to light and allows them to respond to changes in light intensity and wavelength.

The ipRGCs receive light information from the environment and transmit this information to the SCN via the retinohypothalamic tract. This pathway sends direct, monosynaptic connections from the retina to the SCN, bypassing other visual processing areas. The ipRGCs communicate with the SCN, relaying information about light-dark cycles and serving as the primary conduit for optical zeitgeber input.

When light is detected by the ipRGCs, it leads to the suppression of melatonin production from the pineal gland and helps synchronize the internal circadian rhythm with the external light-dark cycle. Light exposure during the day promotes wakefulness and activity, while darkness during the night promotes sleep and rest.

The input from the ipRGCs to the SCN allows the master clock in the SCN to adjust and align the timing of circadian processes throughout the body. This synchronization with the light-dark cycle helps regulate various physiological and behavioral rhythms, including the sleep-wake cycle, hormone secretion, body temperature, and metabolism.

Which physiological parameters that oscillate by internal rhythms in humans do you know?

  1. Sleep-Wake Cycle: The sleep-wake cycle is a prominent circadian rhythm that regulates the alternating patterns of sleep and wakefulness over a 24-hour period.

  2. Body Temperature: Core body temperature follows a circadian rhythm, typically peaking in the late afternoon or early evening and reaching its lowest point during the early morning hours.

  3. Hormone Secretion: Various hormones in the body exhibit circadian fluctuations. For example, cortisol, a stress hormone, typically follows a diurnal pattern with higher levels in the morning and lower levels in the evening. Melatonin, a hormone involved in sleep regulation, is typically released in higher amounts during the evening and nighttime hours.

  4. Blood Pressure: Blood pressure can exhibit diurnal variations, typically showing higher levels during the daytime and lower levels during sleep.

  5. Alertness and Cognitive Performance: Alertness and cognitive performance tend to follow a circadian pattern, with peaks during the daytime and troughs during the early morning hours (commonly known as the "afternoon slump").

  6. Metabolic Processes: Various metabolic processes, such as glucose metabolism and insulin sensitivity, show diurnal variations, with increased activity during the daytime and reduced activity during sleep.

  7. Digestion: The digestive system also demonstrates circadian rhythmicity, with changes in gastrointestinal motility and enzyme secretion across the day.

  8. Cardiovascular Function: Heart rate, cardiac output, and other cardiovascular parameters can exhibit diurnal variations, with higher levels during the day and lower levels during sleep.

Can you think of an example of masking and an example of entrainment of a rhythm from your daily life?


  • Using blackout curtains or wearing a sleep mask: By blocking out external light during sleep, these measures help mask the influence of light on the sleep-wake cycle. They create a darker environment that promotes better sleep and reduces the impact of light as a zeitgeber.

  • Wearing earplugs or using white noise machines: These measures can mask external auditory stimuli, such as noise from traffic or neighbors, which may disturb sleep and impact the quality of rest.

  • Using blue-light blocking glasses: Blue light emitted by electronic devices can interfere with the natural sleep-wake cycle by suppressing melatonin production. Wearing blue-light blocking glasses in the evening can help mask the disruptive effect of blue light and promote better sleep.


  • Morning sunlight exposure: Exposing yourself to natural sunlight in the morning helps entrain your circadian rhythm. The bright light in the morning sends a strong zeitgeber signal to your body, indicating the start of the day and helping you feel more awake and alert. This exposure can regulate your internal clock and promote better daytime functioning.

  • Regular meal times: Consistently eating meals at specific times throughout the day can help entrain the circadian rhythm associated with digestion and metabolism. Regular meal timing signals the body to anticipate and prepare for nutrient intake and promotes better metabolic regulation.

  • Exercise routine: Engaging in regular exercise at consistent times, such as morning or early evening, can help entrain the circadian rhythm associated with physical activity. Regular exercise promotes wakefulness, energy expenditure, and overall well-being, aligning with the natural cycles of the body.

  • Establishing a bedtime routine: Creating a consistent routine before bedtime, such as reading a book or taking a warm bath, helps signal to the body that it's time to wind down and prepare for sleep. This routine can aid in entraining the circadian rhythm associated with sleep onset and improve sleep quality.

Why is it advantageous that individual clock neurons of the SCN have different phases that are synchronized through network connections? Why don’t all cells fire intrinsically at the same phase? Think of the terms “precision” and “robustness” of the clock!

  1. Precision: The variability in phase among individual clock neurons allows for more precise timing and coordination of circadian rhythms. The SCN acts as a central pacemaker, and having a diversity of phases in its constituent neurons helps in accurately timing various physiological and behavioral processes. This diversity ensures that the timing of specific events, such as hormone secretion or sleep-wake cycles, is finely regulated.

  2. Robustness: The presence of different phases in individual clock neurons increases the robustness and stability of the circadian system. If all cells were intrinsically firing at the same phase, the system would be more vulnerable to disruptions. However, by having a range of phases, the SCN can maintain its function even if a subset of neurons is affected or compromised. This redundancy in the system helps ensure that circadian rhythms persist despite external influences or internal variations.

  3. Adaptability: The diversity of phases allows the SCN to adjust and adapt to changes in external cues or environmental conditions. The SCN needs to synchronize its rhythm with the light-dark cycle, and having different phases in its neurons allows for flexibility in entrainment. It enables the system to respond to shifts in light exposure, such as when traveling across time zones, by adjusting the phase relationship among the neurons to align with the new environmental conditions.

In summary, the presence of different phases in individual clock neurons of the SCN contributes to the precision, robustness, and adaptability of the circadian system. This diversity of phases allows for fine-tuning of timing and coordination, enhances the resilience of the system, and enables appropriate adjustments in response to environmental changes.

Through which routes can the master clock in the SCN control the circadian rhythm of peripheral organs or of other brain regions that control behavior?

  1. Neural Pathways: The SCN sends neural signals to other brain regions involved in controlling behavior and physiological processes. It projects to areas such as the pineal gland, which regulates melatonin production, and the hypothalamus, which influences hormone secretion and various homeostatic functions.

  2. Hormonal Pathways: The SCN regulates the release of certain hormones that can impact peripheral organs and brain regions. For example, the SCN controls the timing of cortisol release from the adrenal glands, which influences metabolism and stress response. It also influences the release of other hormones, such as growth hormone and prolactin.

  3. Autonomic Nervous System: The SCN can modulate the activity of the autonomic nervous system, which controls functions such as heart rate, blood pressure, and digestion. By influencing autonomic outflow, the SCN can indirectly regulate the physiological processes of peripheral organs.

  4. Circadian Clocks in Peripheral Organs: The SCN can synchronize or entrain the circadian clocks present in peripheral organs. Peripheral organs, including the liver, kidneys, and gastrointestinal system, have their own internal clocks that are influenced by the SCN. The SCN can send timing signals to peripheral clocks via neural, hormonal, or other signaling pathways, ensuring coordination and alignment of circadian rhythms throughout the body.

These routes of control allow the SCN to exert its influence on peripheral organs and brain regions involved in behavior and physiological regulation. The SCN acts as the central pacemaker, coordinating and synchronizing circadian rhythms across the body, ensuring proper timing and integration of various biological processes.

Explain the combinatorial role of individual taste cells!

  • Type I cell: comprise approximately half the total number of cells in a taste bud. They have narrow, irregularly shaped nuclei, are electron-dense and have wing-like cytoplasmic extensions that ensheath other taste bud cells. Type I cells seem to have glia-like functions. They express enzymes and transporters that are required to eliminate extracellular neurotransmitters and ion channels that are associated with the redistribution and spatial buffering of K+.

  • Type II cell: Approximately one-third of the cells in a taste bud are type II cells. These cells function as chemosensory receptors for sugars, amino acids and/or bitter stimuli as they express taste G protein-coupled receptors (GPCRs) and their downstream effectors. Most type II cells express one class of taste GPCR — namely, taste receptor type 1 (T1R) or T2R — and correspondingly respond only to one taste quality (for example, sweet or bitter, but not both. It should be noted that T1R1, T1R2 and T1R3 are often co- expressed in taste bud cells, and, accordingly, responses to both sweet and umami stimuli can be detected in the same cells. The type II cells in a taste bud can differ in their expression of taste GPCRs such that each taste bud can respond to multiple taste stimuli.

  • Type III cell: the least numerous; they represent 2–20% of the cells in a taste bud, and their incidence varies regionally in the oral epithelium. For instance, taste buds on the anterior tongue (fungiform taste buds) often contain no more than a single type III cell, whereas taste buds in the posterior tongue may contain as many as ten. These cells display slender profiles and oblong nuclei. They do not express taste GPCRs but do contain the machinery required to detect sour taste. Type III cells have ultrastructurally recognizable synapses with features such as clear and dense-cored vesicles, SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins and densities in which the membranes of the taste cell oppose nerve fibres. By contrast, type II cells lack synaptic vesicles and communicate with closely apposed afferent fibres via non-vesicular transmitter release (ATP!).

Explain the term “combinatorial code” and “sparse code” and how they are generated.

What are the advantages of each?

  1. Combinatorial Code:

    • Combinatorial code refers to a coding scheme in which multiple elements or features are combined in various combinations to represent different stimuli or concepts. In this coding scheme, individual neurons or groups of neurons selectively respond to specific combinations of features, and the pattern of their activity represents a particular stimulus or concept.

    • For example, in the domain of olfaction (smell), different odorants can activate a large number of olfactory receptors. However, the perception of a specific odor arises from the unique combination of receptors that are activated and the pattern of their activation. Each receptor can contribute to the perception of multiple odors, and the brain interprets the specific combination of activated receptors to identify and discriminate between different smells.

    • The generation of a combinatorial code involves the integration of multiple sensory inputs or features and the subsequent activation of specific neurons or neural populations that are responsive to particular combinations. This coding scheme allows for a high degree of information representation and discrimination, as different stimuli can be distinguished based on the specific combinations of features that are present.

    • Advantages of combinatorial coding include:

      • High information capacity: Combinatorial codes can represent a large number of stimuli or concepts by combining different elements or features in various ways.

      • Discrimination and specificity: Specific combinations of features can be selectively encoded, enabling precise discrimination between similar stimuli.

      • Flexibility: Combinatorial coding allows for flexible and adaptive representation, as the same elements or features can be recombined to represent different stimuli or concepts.

  2. Sparse Code:

    • Sparse code refers to a coding scheme in which only a subset of neurons or neural populations is active or involved in representing a particular stimulus or concept. In sparse coding, the majority of neurons remain inactive, while only a few neurons become highly active in response to a specific stimulus.

    • This coding scheme often occurs when stimuli or concepts are highly specific or distinct. For example, in visual recognition, certain neurons in the visual cortex may respond selectively to specific visual features, such as vertical lines or curves, while remaining unresponsive to other features. The activation of these sparse populations of neurons represents the presence of those specific features in the visual input.

    • The generation of a sparse code involves a process of competition and selection, where only a limited number of neurons with the highest selectivity or responsiveness to a given stimulus become active, while others remain silent.

    • Advantages of sparse coding include:

      • Efficiency: Sparse codes require fewer active neurons, resulting in a more efficient use of neural resources.

      • Noise reduction: By selectively activating only a few neurons, sparse coding can reduce the impact of background noise and increase the signal-to-noise ratio.

      • Robustness: Sparse codes can be more robust to variations or noise in the input, as only specific and highly responsive neurons are involved in representing a stimulus.

  • Overall, combinatorial coding and sparse coding offer different advantages in representing and processing information. Combinatorial coding provides a rich and flexible representation with high information capacity, while sparse coding offers efficiency, noise reduction, and robustness to variations in the input. Both coding schemes contribute to the neural mechanisms that enable perception, cognition, and the interpretation of sensory information in the brain.

Describe the transduction of olfactory signals in olfactory sensory cells of mammals and insects!


  1. Olfactory Receptors: Mammalian OSCs contain specialized olfactory receptor proteins embedded in their cell membranes.

  2. Odorant Binding: Odorant molecules from the environment enter the nasal cavity and dissolve in the mucus, reaching the olfactory epithelium.

  3. Receptor Activation: When odorant molecules bind to specific olfactory receptors on OSCs, it triggers a series of biochemical events.

  4. Signal Transduction: The binding of odorants activates a cascade of intracellular events, involving G-protein coupled receptors and the activation of the enzyme adenylate cyclase.

  5. cAMP Production: Adenylate cyclase produces cyclic adenosine monophosphate (cAMP) as a secondary messenger.

  6. Ion Channel Activation: cAMP opens cyclic nucleotide-gated (CNG) ion channels, allowing an influx of calcium and sodium ions into the OSCs.

  7. Depolarization: The influx of ions depolarizes the OSC, generating an action potential.

  8. Transmission to the Brain: The action potential is transmitted to the olfactory bulb in the brain via the olfactory nerve, where further processing and perception of the odor occur.


  1. Odorant Receptors: Insects possess olfactory sensory neurons (OSNs) that express various odorant receptor proteins.

  2. Odorant Binding: Odorant molecules from the environment enter the sensory hairs or sensilla on the insect's antennae.

  3. Receptor Activation: When an odorant molecule binds to a specific odorant receptor on an OSN, it initiates a signaling process.

  4. Ion Channel Activation: Odorant receptor activation triggers the opening of ligand-gated ion channels, such as cyclic nucleotide-gated (CNG) or ionotropic receptors.

  5. Ion Flux: The ion channels allow the influx of calcium and/or sodium ions into the OSN, depolarizing the cell.

  6. Action Potential Generation: Depolarization leads to the generation of an action potential in the OSN.

  7. Transmission to the Brain: The action potential travels along the axon of the OSN, forming synapses in the insect's antennal lobe or other higher brain regions, where the olfactory information is processed.

While the overall process of transducing olfactory signals involves receptor activation, ion channel opening, depolarization, and transmission to the brain in both mammals and insects, the specific molecular mechanisms and the anatomical structures involved differ between the two groups.

What is an olfactory glomerulus, where is it located and what is its function?

  • Location:

    Olfactory glomeruli are located in the olfactory bulb, which is a region of the brain directly above the nasal cavity.

  • Structure:

    Each olfactory glomerulus is a spherical cluster of nerve terminals and synapses formed by the axons of olfactory sensory neurons.

  • Organization:

    Olfactory glomeruli are arranged in a distinct pattern within the olfactory bulb, forming a spatial map or glomerular layer.

  • Function:

    The main function of olfactory glomeruli is to serve as convergence sites for information from specific types of olfactory sensory neurons that express the same olfactory receptor.

  • Odor Encoding:

    When odorant molecules bind to specific olfactory receptors on the olfactory sensory neurons, the corresponding glomeruli associated with those receptors are activated.

  • Spatial Representation:

    Olfactory glomeruli contribute to the spatial representation and mapping of different odorant molecules in the olfactory bulb, allowing the brain to distinguish and discriminate between various smells.

  • Processing:

    Within each glomerulus, there are complex interactions between the incoming olfactory sensory neuron axons and the dendrites of second-order neurons (mitral and tufted cells), which process and integrate olfactory information.

  • Projection:

    After processing in the olfactory bulb, information from the olfactory glomeruli is further transmitted to higher brain regions involved in olfactory perception and interpretation.

In summary, olfactory glomeruli are specialized structures in the olfactory bulb that receive and process olfactory information, contributing to the spatial representation and integration of different smells in the brain.

How can humans distinguish more than 10,000 odors with only 400 different odorant receptors?

  1. Combinatorial Coding: The combination of different odorant receptors can generate a vast number of unique receptor activation patterns. The brain can interpret and discriminate between these patterns to perceive distinct odors. By employing combinatorial coding, where different receptors can be activated in various combinations, the olfactory system can generate a larger odor space than the number of individual receptors.

  2. Receptor Sensitivity: Odorant receptors are not limited to responding to a single odorant molecule but can have a degree of sensitivity and respond to multiple structurally similar odorants. This broadens the range of odors that can be detected and distinguished.

  3. Amplification and Signal Integration: The olfactory system has mechanisms to amplify and integrate signals. Even a weak activation of a specific receptor can be amplified through downstream signaling processes, enhancing the detectability of subtle differences between odors.

  4. Temporal Patterns: Odor perception is not solely based on the activation of individual receptors but also relies on temporal patterns of activity. Different odors can evoke distinct patterns of activation across populations of receptors over time, contributing to odor discrimination.

  5. Olfactory Memory and Learning: Human olfactory perception is influenced by olfactory memory and learning. Experience and exposure to different odors can shape and refine the brain's ability to discriminate between them, enhancing odor discrimination abilities beyond what can be achieved solely based on the number of receptors.

What are the advantages of Drosophila melanogaster as a model organism for olfactory research?

  1. Genetic Manipulation: Fruit flies have a well-established toolkit for genetic manipulation. They have a short generation time, a large number of offspring, and well-characterized genetics, making it easier to study the role of specific genes and manipulate their expression in the olfactory system.

  2. Simple and Accessible Olfactory System: The olfactory system of fruit flies is relatively simple compared to mammals, yet it shares fundamental principles with higher organisms. The fly's olfactory system consists of defined anatomical structures, making it easier to study and understand the underlying neural circuits and molecular mechanisms involved in olfaction.

  3. Behavioral Assays: Fruit flies exhibit robust and easily measurable olfactory behaviors, such as olfactory-mediated attraction, aversion, or learning and memory. These behaviors can be readily studied using simple behavioral assays, allowing for high-throughput screening and analysis of olfactory responses.

  4. Neuroanatomy and Connectome: The detailed neuroanatomy and connectome of the fruit fly brain, including the olfactory circuits, have been extensively mapped. This provides a valuable resource for understanding the organization and connectivity of the olfactory system, aiding in the investigation of odor processing and circuit function.

  5. Conservation of Key Olfactory Genes: Many of the key genes and signaling pathways involved in olfaction are highly conserved between fruit flies and mammals. Discoveries made in fruit flies regarding olfactory mechanisms and genes often have relevance and applicability to other organisms, including humans.

  6. Cost and Space Efficiency: Fruit flies are small, require minimal space and resources for maintenance, and have a short lifespan. These factors make large-scale studies feasible and cost-effective, enabling researchers to perform extensive genetic and behavioral analyses.

The combination of genetic tractability, well-defined olfactory system, behavioral assays, neuroanatomical knowledge, genetic conservation, and efficiency make Drosophila melanogaster an excellent model organism for investigating the fundamental principles of olfaction and advancing our understanding of olfactory mechanisms in both flies and higher organisms.

Which parts of the brain regulate sleep phases?

Classical experiments by Moruzzi and Magoun:

  • Electrical stimulation of the midbrain reticular formation promotes the waking state. Damage to this region causes a comatose state.

  • The midbrain reticular formation is normally inhibited by a neuronal system in the medulla oblongata. Disconnecting this inhibition by disconnecting transecting the brain stem at the level of the pons produces a mostly awake animal.

Conclusion: There are wake-promoting neurons and sleep-promoting neurons that interact with each other.

  • Stimulation of the posterior hypothalamus, rostral to the midbrain produces an arousal that resembles stimulation of the midbrain. These neurons release the transmitter histamine. Destruction of these histaminergic neurons increase sleep. Antihistaminic drugs promote sleep (see below: more recent data show that hypocretin (= orexin) is also an important transmitter).

  • Stimulation of the anterior hypothalamus and the adjacent basal forebrain induces sleep. Lesions produce a reduction in sleep. These neurons release the inhibitory transmitter GABA.

Conclusion: Sleep & wake are controlled by different parts of the brain

Sleep initiation: Mediated by the GABA-ergic, inhibitory neurons in the anterior hypothalamus called Non- REM-on cells. They start the Non- REM sleep (see middle column left, Non-REM-on cells)!

They inhibit the histaminergic cells of the posterior hypothalamus and cells of the nucleus reticulates pontis oralis in the midbrain that mediate arousal. Non-REM-on cells are active durinbg Non-REM sleep and inactive during REM sleep and waking.

Conclusion: Non-REM sleep is induced by cells that are inactive during wake and REM sleep. These states exclude each other.

Non-REM sleep initiation: Mediated by the GABA-ergic, inhibitory neurons in the anterior hypothalamus called Non- REM-on cells. They start the Non- REM sleep (see middle column left, Non-REM-on cells)!

They inhibit the histaminergic cells of the posterior hypothalamus and cells of the nucleus reticularis pontis oralis (around the thalamus) in the midbrain that mediate arousal. Non-REM-on cells are active durinbg Non-REM sleep and inactive during REM sleep and waking.

Conclusion: Non-REM sleep is induced by cells that are inactive during wake and REM sleep. These states exclude each other.

Non-REM sleep is characterized by EEG spindles and slow waves, produced by synchronized cortical neurons. These synchronizations are generated by rhythmic firing of thalamic relay neurons that project to the cortex. The rhythmic firing results from the actions of GABA-ergig neurons in the nucleus reticularis.

Why? The rhythmic firing of thalamic and cortical cells occludes the transmission of sensory information through the thalamus and the cortex!

Conclusion: Non-REM sleep is induced by cells that are inactive during wake and REM sleep. Sensory input to the cortex is blocked.

REM sleep is characterized by low- voltage EEG without spindles and slow waves, i.e., not synchronized cortical neurons.

REM-on cells are part of the midbrain arousal system. They activate the GABA-ergic neurons of the nucleus reticularis, and these cannot generate rhythmic bursts anymore. Thereby, cortical cells cannot become synchronized any more. Asynchronously firing thalamo-cortical cells are visible as low-voltage EEG.

The major brain regions controlling REM sleep are visible in the sagittal section across the brain stem and forebrain.

Nuclei in the pontine region (= pons) critical for triggering REM sleep are shown in a coronal section: nucleus reticularis pontis oralis / caudalis (RPO / RPC).

Lesions of the regions block REM sleep or components of REM sleep.

Neurons located in the RPO/RPC trigger the switch from Non-REM to REM sleep.

Three classes: a) PGO-on cells (fire in bursts to initiate PGO spikes in cells of the lateral geniculate nucleus). These cells are regulated by b) REM-off cells (cells in the raphe nuclei of the brain stem, release serotonin = 5-HT). They become blocked if REM sleep is induced. REM-waking-on cells fire during waking and during REM sleep. They produce rapid eye movements during REM and head/neck/kimb movements during wakening. REM-on cells inhibit 5-HT cells and noradrenergic neurons in the raphe nucleus and nucleus ceruleus.

What else is measured in polysomnography?

  1. Electrooculography (EOG): This measures eye movements using electrodes placed around the eyes. It helps determine the different stages of sleep, including rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep.

  2. Electromyography (EMG): EMG records muscle activity by placing electrodes on the chin and/or other muscles. It helps identify muscle tone changes, such as muscle atonia during REM sleep, which is associated with normal paralysis during dreaming.

  3. Electrocardiography (ECG/EKG): ECG measures the electrical activity of the heart. It records heart rate, rhythm, and any abnormalities during sleep.

  4. Respiratory Parameters: Various measurements are taken to assess breathing patterns and respiratory effort during sleep. These may include:

    • Nasal and oral airflow: Monitors the flow of air through the nose and mouth.

    • Thoracic and abdominal effort: Measures the movement of the chest and abdomen during breathing.

    • Oxygen saturation (SpO2): Monitors the level of oxygen in the blood.

    • Capnography: Measures the concentration of carbon dioxide in exhaled breath.

  5. Snoring: Microphones or sensors can be used to detect and record snoring sounds, which may provide insights into the presence of sleep-disordered breathing.

  6. Body Position: Sensors or video monitoring may be employed to track body position changes during sleep, as some sleep disorders can be position-dependent.

  7. Limb Movements: Leg movements, such as periodic limb movements of sleep (PLMS) or restless legs syndrome (RLS), can be recorded using sensors placed on the legs.

What does the term “memory consolidation” mean? How is that related to sleep?

Strong evidence that during sleep replay of neuronal patterns promotes consolidation of memory.

Memory consolidation refers to the process by which newly acquired information and experiences are stabilized and stored in long-term memory. It involves the transformation of initially fragile and labile memories into more stable and enduring forms.

Sleep plays a crucial role in memory consolidation. During sleep, particularly during the deeper stages of non-rapid eye movement (NREM) sleep and the rapid eye movement (REM) sleep stage, the brain undergoes processes that enhance memory consolidation.

Overall, sleep, and its distinct stages, provide a conducive environment for memory consolidation. By replaying and reorganizing newly acquired information, enhancing synaptic connections, and promoting the interaction between key brain regions, sleep contributes to the formation of durable and retrievable memories. Insufficient or disrupted sleep can impair memory consolidation and affect learning abilities.

a) Population coding of place cells within an environment. During spontaneous exploration of an environment, place cells are activated in their relative place fields (colored circles), with some cells coding for overlapping location (firing activity represented below). The location of the animal in the right part of the environment is given by the activity of the population composed of neurons 3, 4 and 5.

(b) In subsequent sleep, and mostly at time of harp wave ripples (notified by blacks stars above LFP signal), reactivations of place cells activated during previous exploration occur (Note that there is still no direct evidence that each SPW-Rs is associated with a reactivation). Since the correlation pattern is strongly maintained during SPW-Rs occurring during the first hour of subsequent sleep, the detection of the firing activity of one specific place cell (#4) can be used to associate intracranial stimulation to the whole cell assembly coding for the related location.

(c) Schematic behavioral output of the association of the engram with a positive valence during sleep. Free exploration of the open field showed homogeneous exploration before pairing. Then during 1 h of sleep, the pairing procedure depicted in panel b. is applied with electrical rewarding stimulation. At awakening, mice went directly towards the place field of the previously paired neuron, and thus to the location represented by the cell assembly it belongs to in this particular context.

Can you explain why slow brain waves occur during deep sleep phases? How do they

originate, and what is the effect?

Slow brain waves, specifically the slow-wave activity (SWA) characterized by slow oscillations known as delta waves (0.5 to 4 Hz), are prominent during the deep sleep stages, also known as slow-wave sleep (SWS). The occurrence of slow brain waves during deep sleep phases is associated with several factors:

  1. Thalamocortical Network: Slow waves during deep sleep arise from the synchronized activity of neurons in the thalamus and cortex. The thalamus acts as a pacemaker, generating rhythmic activity that is then propagated to the cortex. The thalamocortical network plays a crucial role in the generation and propagation of slow oscillations.

  2. Neuronal Synchronization: During deep sleep, there is a high degree of synchronization among neurons in the thalamocortical network. This synchronization is facilitated by inhibitory mechanisms that suppress neuronal activity, leading to the slow, synchronized oscillatory pattern seen in delta waves.

  3. Sleep Homeostasis: Slow waves are influenced by sleep homeostasis, reflecting the need for restorative sleep. The amplitude and frequency of slow waves are related to prior wakefulness and sleep pressure. The longer an individual has been awake, the higher the SWA and the greater the occurrence of delta waves during subsequent sleep.

The effects of slow brain waves during deep sleep are believed to be associated with the restorative functions of this sleep stage:

  1. Memory Consolidation: Slow-wave sleep is associated with memory consolidation, particularly for declarative memories. The synchronization of neuronal activity during slow waves supports the reactivation and consolidation of recently acquired information.

  2. Physiological Restoration: Deep sleep, characterized by slow waves, is associated with physiological restoration. It is believed to promote physical recovery, including the repair and rejuvenation of various bodily systems, consolidation of immune function, and hormone regulation.

  3. Energy Conservation: Slow-wave sleep is associated with reduced metabolism and energy conservation. The synchronized slow oscillations require less energy compared to the more active wakeful or REM sleep states. This energy conservation may allow resources to be allocated for other essential physiological processes.

In summary, slow brain waves, specifically delta waves, are a hallmark of deep sleep stages. They arise from synchronized activity within the thalamocortical network and reflect the restorative and energy-conserving functions of deep sleep. These slow waves are implicated in memory consolidation, physiological restoration, and the overall maintenance of health and well-being.

How is sound converted into neuronal excitation?

  1. Sound Waves: Sound waves are mechanical vibrations that propagate through a medium, such as air or water. When an external sound source, such as a musical instrument or a voice, creates vibrations in the air, it leads to the formation of sound waves.

  2. Ear Anatomy: The ear is divided into three main sections: the outer ear, middle ear, and inner ear.

    • Outer Ear: The outer ear consists of the pinna (visible part of the ear) and the ear canal. Its function is to collect and funnel sound waves towards the middle ear.

    • Middle Ear: The middle ear includes the eardrum (tympanic membrane) and a chain of small bones called the ossicles (malleus, incus, and stapes). When sound waves reach the eardrum, they cause it to vibrate. These vibrations are then transmitted to the ossicles.

    • Inner Ear: The inner ear contains the cochlea, a spiral-shaped structure responsible for converting mechanical vibrations into neural signals. The cochlea is filled with fluid and contains specialized hair cells.

  3. Hair Cells: Within the cochlea, there are two types of hair cells: inner hair cells and outer hair cells. These hair cells are sensory receptors that convert mechanical vibrations into electrical signals.

    • Mechanical Transduction: When the ossicles transmit vibrations to the fluid-filled cochlea, it causes movement of the fluid. This movement stimulates the hair cells.

    • Hair Cell Activation: The movement of the fluid bends the hair bundles on the hair cells, which opens ion channels on their surface. This allows ions to enter the cells, generating electrical signals.

  4. Auditory Nerve: The electrical signals generated by the activated hair cells are then transmitted to the auditory nerve. The auditory nerve is a bundle of nerve fibers that carries the electrical signals from the cochlea to the brain.

  5. Auditory Pathway: The auditory nerve fibers transmit the electrical signals from the cochlea to various auditory processing centers in the brain, including the brainstem, thalamus, and auditory cortex. These areas process and interpret the neural signals, allowing us to perceive and understand the sound.

How are different frequencies encoded?

Different frequencies of sound are encoded in the auditory system through a process called tonotopy, which involves the spatial arrangement and response properties of neurons in the cochlea and auditory pathway.

  1. Cochlea: The cochlea, a spiral-shaped structure in the inner ear, plays a vital role in frequency encoding. As sound waves enter the cochlea, they cause different regions of the cochlear partition to vibrate more vigorously depending on the frequency of the sound.

  2. Basilar Membrane: The basilar membrane is a membrane within the cochlea that runs along its length. It varies in stiffness along its length, becoming narrower and stiffer towards the base (near the oval window) and wider and more flexible towards the apex.

  3. Tonotopic Organization: The basilar membrane's stiffness gradient creates a tonotopic organization, where different regions of the membrane are sensitive to different frequencies. High-frequency sounds (e.g., high-pitched sounds) preferentially activate the base of the cochlea, while low-frequency sounds (e.g., low-pitched sounds) primarily stimulate the apex.

  4. Hair Cell Activation: Along the basilar membrane, there are specialized hair cells that are responsible for converting mechanical vibrations into electrical signals. Hair cells are arranged in rows along the cochlear partition and are most sensitive to specific frequencies.

  5. Frequency-Specific Neurons: The electrical signals generated by hair cells are transmitted to neurons in the auditory nerve. These neurons, known as auditory nerve fibers, have characteristic frequencies to which they are most responsive. High-frequency sounds tend to activate nerve fibers near the base of the cochlea, while low-frequency sounds activate fibers closer to the apex.

  6. Auditory Pathway: The frequency-specific information encoded by the auditory nerve fibers is then transmitted through the auditory pathway to higher-level auditory centers in the brain, including the brainstem, thalamus, and auditory cortex. In these areas, further processing and analysis of the frequency information occur, leading to the perception and recognition of different pitches and tones.

In summary, different frequencies are encoded in the auditory system through the tonotopic organization of the cochlea and the corresponding response properties of hair cells and auditory nerve fibers. This tonotopic representation allows the brain to distinguish and interpret various frequencies, contributing to our ability to perceive and differentiate different pitches and tones.

What are otoacoustic emissions and how are they generated?

Otoacoustic emissions (OAEs) are low-level sounds generated by the cochlea in response to auditory stimulation. These sounds can be measured using sensitive microphones placed in the ear canal. OAEs provide valuable information about the functioning of the inner ear, specifically the health and integrity of the outer hair cells.

The generation of otoacoustic emissions involves a process known as cochlear amplification, which is facilitated by the active mechanics of the cochlea.

  1. Outer Hair Cells: The outer hair cells (OHCs) are specialized sensory cells in the cochlea that play a crucial role in the amplification and fine-tuning of auditory signals. These cells are arranged in rows along the basilar membrane of the cochlea.

  2. Cochlear Amplifier: When sound waves enter the cochlea, they cause vibrations along the basilar membrane. This mechanical energy displaces the hair bundles of the OHCs, activating them.

  3. Feedback Loop: The OHCs are connected to the tectorial membrane above them, forming a feedback loop. When the OHCs are activated by the mechanical vibrations, they undergo changes in length and stiffness.

  4. OHC Motility: The activation of OHCs triggers a process called electromotility or OHC motility. This process involves changes in the cell's length, which results in the active amplification of the traveling wave along the cochlea.

  5. Emission Generation: The amplification produced by the active motility of the OHCs leads to a regenerative feedback loop within the cochlea. This feedback loop generates low-level sounds, known as otoacoustic emissions, which can be detected in the ear canal.

It's important to note that otoacoustic emissions can be classified into different types based on their characteristics. Spontaneous otoacoustic emissions (SOAEs) occur without any external stimulation and are present in a subset of individuals without hearing loss. Evoked otoacoustic emissions (EOAEs) are elicited by specific auditory stimuli, such as clicks or tones.

Otoacoustic emissions serve as a valuable clinical tool for assessing the function of the cochlea, particularly the outer hair cells. They are used in diagnostic audiology to evaluate hearing sensitivity, screen newborns for hearing disorders, and monitor the effects of certain medications or noise exposure on the auditory system.

Which parameters are used to located the source of a sound stimulus?

  1. Interaural Time Difference (ITD): ITD refers to the difference in the arrival time of a sound at each ear. When a sound source is off-center, the sound reaches one ear slightly before it reaches the other ear. The brain uses this time difference to estimate the azimuth (horizontal angle) of the sound source.

  2. Interaural amplitude Difference (ILD): ILD, also known as interaural intensity difference, pertains to the difference in sound intensity or level between the ears. When a sound source is off-center, the head acts as a barrier, causing a shadowing effect that reduces the sound level reaching the far ear. The brain uses this level difference to estimate the azimuth of the sound source.

  3. Spectral Cues: Spectral cues involve the frequency content and filtering of sounds that reach the ears. As sound waves interact with the head and outer ears, certain frequencies are selectively attenuated or enhanced, creating spectral cues that can aid in sound localization.

    • Head-Related Transfer Function (HRTF): HRTF refers to the filtering effect of the head, pinnae (external ears), and torso on incoming sound. The unique filtering characteristics for different sound directions provide spectral cues that help determine the elevation (vertical angle) and front-back location of a sound source.

  4. Monaural Cues: Monaural cues are cues that can be perceived by one ear alone and provide information about the location of a sound source.

    • Spectral Notches: Certain frequencies may be attenuated or suppressed when sound waves interact with the shape of the outer ear and ear canal. These spectral notches can serve as monaural cues for sound localization.

  5. Head Movements: Active head movements are a crucial parameter for sound localization. By moving the head, an individual can obtain dynamic auditory information that aids in determining the direction and location of a sound source.

The brain integrates these auditory cues, including ITD, ILD, spectral cues, monaural cues, and head movements, to create a spatial representation of sound. This allows us to perceive the direction, distance, and position of a sound source in our environment.

How are the receptive fields of ON-center and OFF-center bipolar cells generated?

  1. Cone Photoreceptors: The retina contains three types of cone photoreceptor cells: red-sensitive cones, green-sensitive cones, and blue-sensitive cones. These cones are responsible for detecting different wavelengths of light and initiating the visual signal.

  2. Horizontal Cells: Horizontal cells are interneurons in the retina that play a role in lateral inhibition, which enhances contrast and sharpens visual information. Horizontal cells receive input from multiple photoreceptor cells and provide lateral inhibition to nearby cells.

  3. ON-Center Bipolar Cells:

    • Excitatory Connection: ON-center bipolar cells receive direct synaptic input from the central region of cone photoreceptor cells through their dendrites. When light falls on the central region of the receptive field, it leads to depolarization of the cone cells and subsequent depolarization of the ON-center bipolar cell.

    • Inhibitory Connection: Surrounding the central region of the receptive field, there are horizontal cell processes that receive input from the surrounding cone photoreceptor cells. When light falls on the surrounding region, horizontal cells release inhibitory neurotransmitters onto the dendrites of the ON-center bipolar cells, suppressing their activity.

The combination of direct excitatory input from the central cone photoreceptor cells and inhibitory input from horizontal cells results in an ON-center receptive field for these bipolar cells. They are most responsive when light falls on the central region and surrounded by darkness or lower levels of illumination.

  1. OFF-Center Bipolar Cells:

    • Inhibitory Connection: OFF-center bipolar cells receive direct synaptic input from the central region of cone photoreceptor cells. When light falls on the central region, it leads to hyperpolarization of the cone cells and subsequent hyperpolarization of the OFF-center bipolar cell.

    • Excitatory Connection: Surrounding the central region, horizontal cells receive input from the surrounding cone photoreceptor cells. When light falls on the surrounding region, horizontal cells release excitatory neurotransmitters onto the dendrites of the OFF-center bipolar cells, activating them.

The combination of direct inhibitory input from the central cone photoreceptor cells and excitatory input from horizontal cells results in an OFF-center receptive field for these bipolar cells. They are most responsive when light falls on the surrounding region and the central region is darker.

What is the role of horizontal cells?

Horizontal cells are interneurons found in the retina, playing a vital role in modulating the visual signals transmitted from photoreceptor cells to bipolar cells and retinal ganglion cells.

  1. Lateral Inhibition: Horizontal cells mediate lateral inhibition, which is a process that enhances contrast and sharpens visual information. This process allows the visual system to distinguish between light and dark regions more effectively.

    • Surround Inhibition: Horizontal cells receive input from multiple photoreceptor cells within their receptive field and provide inhibitory feedback to neighboring photoreceptor cells. This feedback inhibits the transmission of signals from the surround region, reducing their activity. This mechanism helps accentuate the contrast between light and dark areas in the visual scene.

  2. Modulating Receptive Fields: Horizontal cells contribute to shaping the receptive fields of bipolar cells and retinal ganglion cells by providing inhibitory or modulatory input. They influence the center-surround organization of receptive fields, which is important for detecting edges and contours in the visual scene.

    • Receptive Field Surround: Horizontal cells send lateral inhibitory connections to the dendrites of bipolar cells and retinal ganglion cells, affecting their responses to light stimuli. By inhibiting the surround region of the receptive field, horizontal cells help refine the center-surround organization of receptive fields and enhance the detection of edges and spatial details.

  3. Spatial Integration and Contrast Enhancement: Horizontal cells integrate signals from neighboring photoreceptor cells and modulate their activity to improve the spatial integration and processing of visual information.

    • Spatial Summation: By receiving input from multiple photoreceptor cells within their receptive fields, horizontal cells perform spatial summation, which allows for broader integration of signals over a larger area. This integration helps in the detection and processing of visual features and enhances the sensitivity to low-contrast stimuli.

  4. Adaptation to Light Levels: Horizontal cells contribute to the adaptation of the retina to different light levels. They can adjust the strength of inhibitory feedback based on the overall level of illumination, allowing the retina to function optimally across a wide range of light conditions.

Overall, horizontal cells play a crucial role in lateral inhibition, modulation of receptive fields, spatial integration, and contrast enhancement in the retina. By influencing the interaction between photoreceptor cells, bipolar cells, and retinal ganglion cells, horizontal cells contribute to the processing and refinement of visual signals before they are transmitted to higher visual processing centers in the brain.

How are the receptive fields of retinal ganglion cells generated?

  1. Photoreceptor Cells:

    The retina contains two main types of photoreceptor cells—rods and cones. Rods are more sensitive to dim light, while cones are responsible for color vision and work best in brighter light conditions.

  2. Convergence:

    Multiple photoreceptor cells (either rods or cones) converge onto a single retinal ganglion cell. The level of convergence varies across retinal ganglion cell types, influencing the receptive field properties.

  3. Center-Surround Organization:

    The receptive fields of retinal ganglion cells typically exhibit a center-surround organization. Within each receptive field, there is a central region (center) and a surrounding region (surround).

  4. ON-Center and OFF-Center Cells:

    • ON-Center Cells: For ON-center retinal ganglion cells, the center of the receptive field is more sensitive to light increments or increases in illumination. Stimulation of the central region with light results in increased firing rates.

    • OFF-Center Cells: For OFF-center retinal ganglion cells, the center of the receptive field is more sensitive to light decrements or decreases in illumination. Stimulation of the central region with light results in decreased firing rates.

  5. Lateral Inhibition: Horizontal cells, interneurons in the retina, provide lateral inhibitory connections that influence the receptive fields of retinal ganglion cells.

    • Surround Inhibition: The surround region of the receptive field, which receives input from photoreceptor cells outside the central region, is affected by inhibitory connections mediated by horizontal cells. When light is presented to the surround region, it leads to inhibitory feedback from horizontal cells onto the retinal ganglion cell, suppressing its activity.

The combination of convergent input from photoreceptor cells, the spatial arrangement of excitatory signals in the central region, and inhibitory feedback from the surround region shapes the receptive fields of retinal ganglion cells. This center-surround organization enhances the detection of contrast, edges, and spatial details in the visual scene.

Explain how receptive fields of neurons of the primary visual cortex are generated that show orentation selectivity.

  1. Retinal Ganglion Cells:

    Retinal ganglion cells transmit visual information from the retina to the primary visual cortex. Different types of ganglion cells respond preferentially to specific orientations of visual stimuli.

  2. Orientation Columns:

    Within the primary visual cortex, neurons are organized into columns that exhibit preference for different orientations. These orientation columns span multiple cortical layers and are responsible for encoding various orientations.

  3. Simple Cells:

    Simple cells are neurons found in V1 that exhibit orientation selectivity. They respond maximally to visual stimuli with a specific orientation, such as horizontal, vertical, or tilted orientations.

  4. Lateral Connections:

    Lateral connections between neurons within the visual cortex play a crucial role in generating receptive fields with orientation selectivity.

    • Excitatory and Inhibitory Interactions:

      The receptive fields of simple cells are formed through a combination of excitatory and inhibitory inputs from neighboring neurons. These lateral interactions are mediated by inhibitory interneurons, such as the parvalbumin-expressing (PV) interneurons.

    • Center-Surround Organization:

      The receptive fields of simple cells exhibit a center-surround organization, similar to the receptive fields of retinal ganglion cells. However, the interactions between the excitatory and inhibitory inputs from neighboring neurons result in more precise orientation selectivity.

    • Preferred Orientation:

      The orientation selectivity of simple cells arises from the specific spatial arrangement of the excitatory and inhibitory inputs. The presence of properly aligned excitatory and inhibitory inputs allows the neuron to respond maximally to a specific orientation and exhibit less response to orientations orthogonal to its preferred orientation.

The combination of inputs from retinal ganglion cells, lateral interactions within the visual cortex, and the organization of orientation columns leads to the generation of receptive fields with orientation selectivity in the primary visual cortex. These receptive fields are responsible for encoding and processing visual information related to the orientation and contours of objects in the visual scene.

Describe the connectivity between retinal ganglion cells and layers of the lateral geniculate nucleus. Which cell types do you know, and to which visual parameters do they primarily respond?

  1. Parvocellular (P) Pathway:

    • P Ganglion Cells: P ganglion cells, also known as midget ganglion cells, project their axons predominantly to the parvocellular layers of the LGN (layers 3-6).

    • Visual Parameters: P cells primarily respond to fine spatial details, color vision, and slower temporal changes. They play a significant role in high-resolution visual processing, such as identifying object features and color discrimination.

  2. Magnocellular (M) Pathway:

    • M Ganglion Cells: M ganglion cells project their axons primarily to the magnocellular layers of the LGN (layers 1 and 2).

    • Visual Parameters: M cells are more sensitive to high temporal frequencies, motion detection, and overall contrast. They contribute to the perception of motion, depth, and global aspects of visual scenes.

  3. Koniocellular (K) Pathway:

    • K Ganglion Cells: K ganglion cells, also referred to as small bistratified cells, project their axons to the koniocellular layers of the LGN, which are interwoven between the main layers.

    • Visual Parameters: The specific visual parameters primarily encoded by K cells are not as well understood as the P and M pathways. However, studies suggest their involvement in color processing, blue-yellow color opponency, and certain aspects of visual perception.

The segregation of retinal ganglion cell types and their projections to different layers of the LGN allow for parallel processing of visual information along distinct pathways. This organization preserves the separation of various visual parameters and contributes to the perception of different visual features, such as color, spatial details, motion, and contrast. The LGN acts as a crucial relay station, transmitting visual signals from the retina to higher visual areas, including the primary visual cortex (V1), where further processing and integration of visual information occur.

Please explain how THC, opium, cocaine and nicotine act on the dopaminergic system!

Opioids encompass a large group of naturally occurring (e.g., morphine), semi- natural (e.g., heroin), and synthetic (e.g., methadone) substances).

Opioids act as analgesics (“painkillers”) on the central nervous system.

Opioids bind on specific G-protein coupled receptors (opioid receptors), discovered in 19731. Opioid receptors are distributed widely in the brain, in the spinal cord, on peripheral neurons, and digestive tract. There are several classes: mu, kappa, delta (see table), zeta, and nociceptine receptor.

Drugs of abuse (heroin, morphine, etc.) act on the mu (μ) receptors (three types).

Opium (dried latex obtained from the seed capsules of the opium poppy) contains several alkaloids (phenantrenes), e.g., morphine, codeine, thebaine. Chemical acetylation produces heroine.

Effects of nicotine: anti-fatigue, stimulant-like, anti-anxiety effects. Improves cognitive performance in animals and humans.

Has direct reinforcing effects: intravenous self-administration experiments in animals!

Acts as a direct agonist of nicotinic acetylcholine receptors.

The addictive effect is attributed to the activation of nicotinic acetylcholine receptors on mesolimbic dopaminergic neurons (VTA and nucleus accumbens). Knockout of acetylcholine receptors on dopaminergic neurons stops nicotine self- administration.

Again: the dopaminergic system is the target of the drug and causes addiction.

THC: There are two types of cannabinoid receptors, CB1 and CB2.

CB1 is expressed in the brain, most pronounced in cerebellum, hippocampus, basal

ganglia, but also in the enteric nervous system.

CB2 is mostly expressed in immune cells and cells involved in bone formation (osteoclasts and osteoblasts).

Endocannabinoids are anandamide, γ-linolenoylethanolamide, etc.

THC triggers dopamine release through binding to CB1 receptors on VTA dopaminergic neurons.

Huntington‘s disease (HD)

Often, neurodegenerative diseases are caused by genetic predispositions (multi- factorial) and environmental factors (lifestyle, nutrition, exercise, etc.).

But Huntigton’s disease is an inherited, genetic disease, caused by a mutation in the Huntingtin gene.

Huntington’s disease also called Chorea Huntington (old German name: Veitstanz).

Symptoms of Huntington‘s disease

Prevalence: 2,7 persons per 100.000 (5,7 : 100.000 in Europe); fully penetrant (all carrier of the mutation will get the disease); ~ 10.000 patients in Germany.

First symptoms typically at the age of ~ 40 years. Depends on extension of glutamine repeats. Death on average 15 years after first symptoms. Progressive development of sereneness of symptoms.

  • Involuntary, uncontrollable movements (jerking, writhing) (chorea; greek for dancing)

  • Difficulties with speech, chewing and swallowing

  • Slow and abnormal eye movements

  • Impaired gait, posture, balance

  • Rigidity of muscles, contractions

  • Abnormal face expressions

  • Progressive impairment of cognitive abilities (e.g., planning, exhibition of inappropriate movements, cognitive flexibility, abstract thinking, ...)

  • Memory deficits

  • Neuropsychiatric manifestations, e.g., anxiety, aggression, depression compulsive behavior like addiction, etc.

Mutated gene: Huntingtin on human chromosome 4.

Novel mutation rare.

50% chance of getting the disease if one parent is carrier.

Men and women equally affected.

The mutation of the Huntingtin gene is very distinctive: There are too many repeats in the bases CAG, encoding the amino acid glutamine

(abbreviation for glutamine: Q).

If there are too many repeats of CAG, a poly glutamine chain arises that causes Huntington’s disease. Huntigton’s disease is a poly-Q-disease!

What exactly is a Lewy body?

Aggregated α-synuclein in Lewy bodies resembles the changes in cooking an egg: The function in the brain for α-synuclein remains unclear. However, when α-synuclein is found aggregated (also known as denatured) in the mid-brain substantia nigra it contributes to Parkinson’s. α-Synuclein is a protein, and sometimes unusual forces cause proteins to interact in a detrimental manner, and in this case by aggregation of α-synuclein to create the Lewy body.

Lewy bodies are abnormal protein aggregates that develop inside nerve cells (neurons) in certain areas of the brain. These abnormal protein clumps are a hallmark feature of several neurodegenerative disorders, including:

  1. Dementia with Lewy Bodies (DLB): DLB is a type of progressive dementia that shares characteristics with both Alzheimer's disease and Parkinson's disease. Individuals with DLB often experience cognitive impairments, visual hallucinations, fluctuating alertness, and motor symptoms resembling those of Parkinson's disease, such as tremors and stiffness. The presence of Lewy bodies in the brain is a key pathological feature of DLB.

  2. Parkinson's Disease (PD): While Parkinson's disease is primarily characterized by the loss of dopamine-producing neurons in the substantia nigra region of the brain, Lewy bodies can also be found in some cases, especially in certain brain regions outside the substantia nigra. These Lewy bodies may contribute to the motor and non-motor symptoms seen in PD.

Lewy bodies are composed mainly of a protein called alpha-synuclein. In their normal state, alpha-synuclein plays a role in regulating synaptic function within neurons. However, in Lewy body diseases, alpha-synuclein undergoes abnormal changes, leading to the formation of insoluble clumps. These clumps are believed to disrupt normal cellular processes and contribute to the degeneration of neurons.

Why do only dopaminergic neurons degenerate? Please explain one current hypothesis!

High Energy Demands: Dopaminergic neurons have high energy requirements due to their constant firing and release of dopamine. This high energy demand makes them more reliant on efficient mitochondrial function. Mitochondria are cellular organelles responsible for producing energy in the form of adenosine triphosphate (ATP). Dysfunctional mitochondria can lead to reduced energy production and an increased production of ROS.

In Parkinson's disease (PD), a specific type of brain cell called substantia nigra dopamine (SN DA) neurons is particularly vulnerable. These neurons might be at risk because they struggle with energy production. This can happen for a few reasons:

  1. Mitochondrial Problems: Mitochondria are like energy factories in cells. SN DA neurons may have trouble making enough energy (in the form of ATP) due to issues with their mitochondria. They might have fewer or poorly distributed mitochondria, especially in the long extensions (axons) of the neurons, which are the first to degenerate in PD.

  2. Lack of Myelin: SN DA axons also lack a protective covering called myelin, which helps transport energy-supporting substances. This means they might have less access to the materials needed for energy production.

  3. High Energy Demands: SN DA neurons have a tough job. They need a lot of energy to maintain their natural rhythmic firing and to support their extensive network of axons that connect to other parts of the brain.

Because SN DA neurons are already dealing with energy challenges, they might be more sensitive to anything that further disrupts their energy production. This could explain why they are particularly susceptible to problems with their mitochondria, which are a known feature of PD. In essence, these energy-related issues could play a crucial role in why SN DA neurons are especially vulnerable in Parkinson's disease.

How is Parkinson’s disease treated? What are the most severe side effects?

common treatment approaches:

  1. Medications:

    • Dopaminergic Medications: These drugs are the primary treatment for PD. They help increase dopamine levels in the brain. Common medications include levodopa (usually combined with carbidopa), dopamine agonists (e.g., pramipexole, ropinirole), and monoamine oxidase type B (MAO-B) inhibitors (e.g., rasagiline, selegiline).

    • Anticholinergics: These drugs can help manage some motor symptoms.

    • Amantadine: Used to alleviate symptoms like tremors and dyskinesias.

  2. Physical and Occupational Therapy:

    • Physical therapy can help improve mobility and balance.

    • Occupational therapy focuses on daily activities and fine motor skills.

  3. Exercise and Rehabilitation:

    • Regular physical activity can help maintain muscle strength and flexibility.

    • Speech therapy may be necessary for speech and swallowing difficulties.

  4. Surgical Interventions:

    • Deep Brain Stimulation (DBS): In cases of advanced PD with significant motor fluctuations and medication side effects, DBS surgery may be considered. It involves implanting electrodes in specific brain regions and is used to modulate abnormal neural activity.

common side effects include:

  1. Dyskinesias: Involuntary, often jerky, movements can occur as a side effect of long-term levodopa use.

  2. Motor Fluctuations: Over time, individuals with PD may experience "on-off" fluctuations, where medications work inconsistently, leading to periods of good symptom control (on) and periods of worsened symptoms (off).

  3. Psychiatric Symptoms: Some PD medications can cause psychiatric side effects such as hallucinations, delusions, and mood changes.

  4. Orthostatic Hypotension: A drop in blood pressure upon standing can lead to dizziness and falls.

  5. Gastrointestinal Issues: Constipation and nausea can be common side effects of PD medications.

  6. Sleep Disturbances: PD can disrupt sleep patterns, and some medications may contribute to sleep problems.


Soli W.


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