What are the differences between Somatic and Autonomic nervous system?
Somatic: only Acetylcholin
Autonomic:
Sympathic division: Acetylcholin + Norepinephrine (and Epinephrine)
Parasympathic division: Acetylcholin + Ganglion
Which organs do the Somatic and Autonomic nervous system affect?
Somatic: skeletal muscle
Autonomic: smooth muscle, glands, cardiac muscle
Which structures are part of the hindbrain?
Myelencelphalon (medulla oblongata) and Metencephalon (cerebellum, pons, reticular formation)
What are the important systems of the reticular formation?
ARAS (Ascending Reticular Activating System) —> regulating wakefulness and sleep-wake circle
PAG (Periaqueductal Gray) —> for pain modulation / relief
What are the functions of the hindbrain parts?
Myelencephalon —> breathing, blood, pressure, vomiting
Metencephalon —> wakefulness, muscle tone, pain, sleep-wake circle
What does substantia nigra do?
releases dopamine to basal ganglia
What are the two divisions of the midbrain / Mesencephalon?
Tectum (dorsal) for visual and auditory reflexes
Tegmentum (ventral) for dopamine release (substantia nigra) and coordination of movement (red nucleus)
What is the meaning behind the name ‘pons’?
bridge between cerebellum and cerebrum
What are the functions of the Thalamus
main integrating centre for sensory information —> gate of consciousness
receives input from basal ganglia and cerebellum
What are functions of Hypothalamus?
main control centre for autonomic nervous system
—> hormone release (endocrine system)
—> circadian clock, hunger, thirst, …
Which parts make up the Forebrain?
Forebrain = Telencephalon + Diencephalon
Diencephalon = Thalamus + Hypothalamus
Telencephalon (limbic system) = Amygdala + Hippocampus + Basal Ganlia
What are the functions of the Amygdala?
part of limbic system
—> pleasure, fear, addiction
—> forming / storing memories of emotional events
What are the functions of the Hippocampus?
—> formation of memories including spatial + navigation
—> damage —> anterograde amnesia
What are functions of Basal Ganglia?
motor control (with motor cortex and thalamus)
—> regulate initiation /termination of movements (substantia nigra -> Parkinson)
—> some role in attention, memory, planning
Overview over division of CNS
List the important neuromodulators in the brain.
Norepinephrin (NE)
Dopamine (DA)
Serotonin (5-HT)
Acetylcholine (Ach)
What are the functions of Norepinephrin (NE)?
attention, arousal (Erregung), stress
produced by Locus coeruleus
What are the functions of Dopamine (DA)?
motivation, curiosity, reward expectation
produced by substantia nigra, N. infundibularis
What are the functions of Serotonin (5-HT)?
sedation, mood, social behaviour, appetite, digestion, sleep, memory, sexual desire
produced by Raphe nuclei
What are the functions of Acetylcholine (Ach)?
focused attention, promoting learning
produced by Basal forebrain
How can the CNS be divided anatomically and chemically?
Anatomically —> clearly identifiable based on phylogenetic and ontogenetic development
chemically —> chemical segregation according to existing neurotransmitters
Name the two groups of Monoamines and some examples.
Catecholamines (e.g Dopamine, Norepinephrine, Epinephrine)
Inolamines (e.g Serotonine, Histamine)
What is the most abundant excitatory neurotransmitter?
Glutamate
Which receptors are associated with the glutamatergic system?
NMDA
AMPA
What pathophysiology are associated with the glutamatergic system?
Alzheimer
Parkinson
Epilepsy
Ischemia
ALS
What is the most abundant inhibitory neurotransmitter?
GABA
What pathophysiology is associated with a disturbance of the GABAergic system?
Anxiety
Depression
Memory
—> Target for Benzodiazepines, Barbiturates, etc.
Where is glutamate involved?
fast neurotransmitting
signalling
forming of memories
How is the nervous system divided?
central: spinal cord & brain
peripheral: rest of body
somatic
autonomic
sympathic -> stress
parasympathic -> relax
What is highly abundant in the peripheral nervous system?
cholinergic system
What pathophysiology is associated with a disturbance of the cholinergic system?
Huntington
Myasthenia gravis (autoimmune disease)
What are important receptors of the cholinergic system?
Nicotinic ACh receptors —> excitatory
Muscarinic ACh receptors —> either inhibitory or excitatory
Where is serotonine mainly produced?
raphe nuclei
What are the functions of the serotonergic system in different areas?
frontal cortex: cognition, memory
hippocampus: memory
other limbic areas: mood
What pathophysiology is associated with a disturbance of the serotonergic system?
Schizophrenia
Migraine
What are receptors of the serotonergic system?
5-HT1 - 5-HT7
Where is the dopaminergic system involved?
Highly involved in substances of abuse like heroin, cannabis, cocaine, nicotine
—> drugs are activating the mesolimbic system via VTA —> NAc
What pathophysiology is associated with a disturbance of the dopaminergic system?
increased dopamine —> hyperkinesis —> Parkinson
imbalance of dopamine conc in telencephalon —> Schizophrenia
Mania
Drug addiction
What are receptors of dopamine?
D1 to D5
D1 and D2 —> involved in Parkinson
D2 and D4 —> involved in Schizophrenia
What are the functions of the adrenergic system in different areas?
Peripheral nervous system: body temperature, blood flow
Central nervous system: attention, consciousness
What pathophysiology is associated with a disturbance of the adrenergic system?
deficit —> Depression
Stress
What are receptors of adrenergic system?
α1, α2
β1, β2, β3
What is the effect of drugs that are inhibiting H1-receptors of the Histaminergic system?
sedation, tiredness
Overview of neuromodulators
Modulator
Acetylcholine
Dopamine
Norepinephrine
Serotonin
Abbr.
ACh
DA
NE
5-HT
Function
learning
reward
stress
attention
mood
Receptor
Nicotinic ACh
Muscarinic ACh
D1-D5
1&2 -> Parkinson
2&4 -> Schizophrenia
alpha1&2
beta1-3
5-HT1 -> 5-HT7
Produced in
basal forebrain
Sustantia nigra
locus coeruleus
Areas
activates meso-limbic system: VTA => NAc
CNS -> attention, consciousness
PNS -> body temp., blood flow
PFC: cognition
other limbic: mood
Diseases
too much:
imbalance:
→ deficit
Migrane
What are the natural rewards of the brain and the involvement of drugs of abuse?
food, water, sex and nurturing
—> feel pleasure
—> reinforce behavior of repetition
—> survival
drugs of abuse hijack physiological reward mechanisms
Describe the reward circuit and which receptors are included.
stimulation of dopaminergic reward system in the mesocorticolimbic dopamine system
VTA (dopamine production) —> NAc (Motivation / goal-directed behavior) —> PFC (Prefrontal cortex)
liking —> wanting —> craving
Receptors:
Glutamate (NMDA, AMPA)
DA (D1, D2)
Serotonin (5-HT1-7)
What is the role of dopamine in the reward circuit?
DP is crucial in memory formation —> motivation to repeat pleasurable memories
What causes VTA to be activated/inhibited in reward circuit?
activated:
rewards
expectation of rewards
unexpected rewards —> very high activation
inhibited:
absence of expected rewards
What is (positive/negative) reinforcement?
stimulus that causes response to be maintained and increased
positive: increases behavioral response to get positive reward (food, sex, …)
negative: increases behavioral response to end punishment (pain, …)
Do drugs of abuse or natural rewards increase Dopamine release in NAc?
drugs of abuse!!!!!
Name three classes of more recent drugs of abuse
Amphetamines (MDMA, …)
GHB/GBL
NPS (novel psychoactive substances) = legal highs
PCP, ketamine
Bath salts (mephedrone, mehylone, …)
How is alkcohol (Ethanol) affecting the VTA-NAc reward circuit?
stimulating GABA-receptor
—> inhibiting GABA neurons
—> no further inhibition of VTA
—> increased activity of NAc
What is the result of chronic drug use?
causes dopamine cells to shrink —> dramatically decreasing reward signals
How is nicotine affecting the VTA-NAc reward circuit?
Nicotine activating nicotinic receptors
producing a desensitization
activating nAChR (nicotinic Acetylcholin receptor)
activating a7-nAChR
—> activating VTA neurons
—> producing enhanced release of Dopamine in NAc
Tolerance, Sensitization, and Dependance.
What causes addiction?
none of them defines it per se!
many none-addictive drugs also cause tolerance, sens, and depend. —> e.g. sugar
Addiction is caused by drug-induced plastic changes in reward or reinforcement
Describe the synaptic plasticity and altered gene expression for 3 cases: Normal reward learning, out of control drug use, dependance
1) Reward learning: (normal process)
normal amount of Dopamine from natural rewards
normal gene transcription for (non-) NMDA receptors in the NAc.
2) Out of control drug use
High dopamine output from drug of abuse
—> increased gene transcription
—> more (non-) NMDA receptors in NAc.
3) Frequent out of control drug use
—> Increased amount receptors
—> lower sensitivity to normal amount of dopamine obtained by natural rewards
How can be addiction be viewed on a neurobiological basis?
disruption/dysfunction of reward pathway
involves inadequate reward signaling from limbic areas
associated with certain behaviors
diminished ability of PFC, CG, OFC
—> no properly responses to emotional information from limbic areas
Are there treatment options?
YEES!
Opioid addiction —> methadone, buprenorphine, naltrexone
Nicotine addiction —> patches, …
Alcohol addiction —> disufiram, acamprosate, naltrextone
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