3 Development of the Nervous System

• 77% water

• 12 % lipids

• 8 % protein

• 2 % soluble organic substances

• 1 % carbohydrates

Weight: 1 and a half bottle of water

• most of the neurons: Cerebellum

  (although it represents only 10% of the weight)

• most of the weight: Cortex

  (In human: cerebral cortex with sulci and gyri – surface 2.600 cm2)

Ratio neurons/non-neurons is different in human and rodent (1:1 vs. 1:4)

1. Cell proliferation

2. Cell migration

3. Cell differentiation

radial glial cells = neural progenitor cells, located in the ventricular zone (near the inner surface of the neural tube))

• initially: symmetric cell division = vertical cleavage

  —> expansion of progenitor cells

• later: asymmetric cell division predominates = horizontal cleavage

  —> daughter cell migrates to the cortex and never divides again

  —> the other daughter cell remains in the ventricular zone to continue dividing

glutamergic migrate radial

• origin in dorsal part of the telencephalon

• lays under the cortex

GABAergic migrate tangential

• origin in ventral part of the telencephalon

• far away from dorsal cortex

• radial glial cells in ventricular zone

• Cajal-Retzius cells in marginal zone

= inside out development of the cerebral cortex

1. layer VI

2. layer V

3. …

—> form the cortical plate

• Reelin (ECM protein, secreted into marginal zone by Cajal-Retzius cells)

Reeler mouse: = Reeler mutant

• cortical plate cannot be fomred

• cells cannot migrate

• inverted layer order

Pia mater

• the cannabinoid CB1 receptor

  • regulates migration of cortical neurons

• the inside-out development is disrupted

• neuronal differentiation

• astrocyte differentiation

• oligodendrocyte differentiation

• source

• timely sequence

• intracellular signals

  • Semaphorine 3A

  • in marginal zone

  • responsible for polarisation e.g. neurons

    —> repels growing axons (causing them to move away from the surface) and attracts apical dendrites (causing them to grow toward the brain's surface)

• NOT in cortex (very old)

• in Hippocampus (crucial for learning and memory)

  • 700 neurons daily (same number we lose every day)

  • too limited to repair CNS damage

The growth cone of an axone

• Filopodia prode the environment and direct the growth of the neurite towards attractive cues

• attracte cues for axons = Netrin

  • secreted by cells of ventral midline

    —-> axons with Netrin receptor grow to midline

• <-> Slit (rejects axone)

  • secreted by cells of ventral midline

    —> axons with Slit receptor (“Robo”) grow away from midline

—> axon grows to the midline until it crosses the midline

—> change of expression (Netrin receptor —> Slit receptor “Robo”)

—> grows away from midline

fasciculation: axons grow together in bundles by adhering to one another with the help of cell adhesion molecules (CAMs)

molecular highways: Laminin and Integrin molecules = ECM = determine growth direction

a growth cone must to get in contact with it´s target

• interaction between proteins secreted by

  • the growth cone = e.g. Agrin

  • the target membrane = e.g. MuSK (Agrin receptor) in muscle cell membrane

    —> ACh receptors in postsynaptic membrane are built via Rapsyn

• dendritic Filopodium contacts an axon (that passes by)

• presynaptic: recruitment of synaptic vesicles + active zone proteins

• postsynaptic: neurotransmitter receptors accumulate

• adhesion molecules are expressed by both presynaptic and postsynaptic membranes

mechanisms that ensure

• stability and speed in the adult human brain (such as myelin and the associated proteins)

• simultaneously block the ability to reorganize and heal after an injury (e.g. specific environment that inhibits axonal growth)

Cells that do not receive enough of survival factors activate a genetic suicide program = apoptosis

• factors e.g. NGF, released by target tissues

—> crucial for precisely matching the number of neurons to the size of the target area

neural connections occur in three phases

• [pathway selection (based on chemical signals)]

• [target selection (based on chemical signals)]

• address selection (based on neuronal activity and synaptic transmission)

  • activity dependence plays a crucial role

  • includes synaptic rearrangement in the end

  • Hebb´sche Regeln

—> only synapses whose activity correlates with that of their target cells persist over time

LTP (long-term potentiation): „Neurons that fire together, wire together“

LTD (long-term depression): „Neurons that fire out of sync, lose their link“

NMDA receptor

—> acts as a coincidence detector for LTP and LTD

Ectoderm —> neural plate —> neural tube —> CNS

Ectoderm —> neural plate —> neural crest —> all neurons with cell bodies in PNS

22 days after conception

= neurulation

• Forebrain

  • Optic vesicle

  • Thalamus / Diencephalon

  • Telencephalon

• Midbrain

• Hindbrain / Rhombencephalon

• Optic vesicle

  • Retina

  • Optic nerve

• Thalamus / Diencephalon

  • Dorsal thalamus

  • Hypothalamus

  • Third ventricle

• Telencephalon

  • Olfactory bulb

  • Cerebral cortex

  • Basal telencephalon

  • Corpus callosum

  • Cortical white matter

  • Internal capsule

  • Lateral ventricles

• Midbrain

  • Tectum

  • Tegmentum

  • Cerebral aqueduct

• Hindbrain (Rhombenecephalon)

  • rostral Hindbrain

    • Cerebellum

    • Pons

    • fourth ventricle

  • caudal Hindbrain

    • Medulla

    • Medullary pyramids

    • fourth ventricle

• White matter columns

• Spinal canal

• Spinal gray matter

  • Dorsal horn

  • Ventral horn

  • Intermediate zone

Telencephalon

• cortex

• basal telencephalon

• olfactory bulb

Diencephalon

• Thalamus

• Hypothalamus

Mesencephalon

• Tectum

• Tegmentum

Hindbrain

• Cerebellum

• Pons

• Medulla

Spinal cord

• lateral ventricles

  • Cerebral cortex

  • Basal telencephalon

  • Thalamus

• third ventricle

  • Thalamus

  • Hypothalamus

• cerebral aqueduct

  • Tectum

  • Tegmentum

• fourth ventricle

  • Cerebellum

  • Pons

  • Medulla

• volume (surface area) of the neocortex has changed

  • Differences in the duration of cell division during development result in a significantly larger surface area of the human cortex compared to other species

• basic structure (layered architecture) remained largely the same

<-> expansion of association areas (Bordmann-Areas) in the human brain as a recent evolutionary trait