The developing nervous system Flashcards
initiation neurulation
week 3: Appearance of the notochord and prechordal mesoderm induces the overlying ectoderm to thicken and form the neural plate –> formation of neuroectoderm is initiation of neurulation
neurulation
- Neurulation is the process whereby the neural plate forms the neural tube:
1. By the end of the third week, the lateral edges of the neural plate become elevated to form neural folds, and the depressed midregion forms the neural groove
2. Gradually, the neural folds approach each other in the midline, where they fuse (begins at somite 5 and moves cranially and causally)
3. Closure of the cranial neuropore occurs at approximately day 25 whereas the posterior neuropore closes at day 28
primary brain vesicles (3 vesicle stage)
Week 4:
- Prosencephalon
- Mesencephalon
- Rhombencephalon
5 vesicle stage
Week 5:
- Telencephalon –> primitive cerebral hemispheres
- Diencephalon –> thalamus, hypothalamus, etc.
- Mesencephalon –> midbrain
- Metencephalon –> pons and cerebellum
- Myelencephalon –> medulla oblongata
neurogenesis in CNS
The brain develops from the walls of the 5 fluid-filed vesicles, in the early stages consisting of 2 layers: 1. The ventricular zone 2. The marginal zone Neurogenesis consists of 3 main steps: 1. Cell proliferation 2. migration 3. differentiation
neurogenesis step 1
Cell proliferation:
- Cell in VZ extends a process which attaches to the pial surface
- DNA is replicated in the MZ
- The cell now has 2 copies of the genome
- Cell retracts arm from pial surface and moves back to VZ
- Cell now divides in a symmetrical (horizontal) or asymmetrical (vertical) way (depends on notch)
neurogenesis step 2
Cell migration:
- After division the daughter cells migrate along thin fibers emitted by radial glial cells that span the distance between the VZ and the pia mater
- This way the neural precursor cells can reach the surface of the brain
- They accumulate at the subplate where they start to differentiate and then form the 6 brain layers
neurgenesis step 3
Cell differentiation –> notch signalling regulates the fate of cells in the developing cerebral cortex
1. Neuronal differentiation –> Primarily prenatal
2. Astrocyte –> Peaks around time of birth
3. Oligodendrocyte
(notch inhibits neuronal precursors from becoming neurons, notch causes glial precursors to become astrocytes when there is no notch the glial precursors becomes an oligodendrocyte)
neurotrophic signalling
Neurons extend their axons to target cells which secrete low levels of neurotrophic factors –> promote neuronal survival via transcription of pro-survival genes
Neurons that fail to receive adequate amounts of neurotrophic factors die through apoptosis
Nerve growth factor is a very important neurotrophic factor
Neurotrophins binds mostly to tyrosine kinase receptors (Trk) –> regulate synaptic strength and plasticity
synapse formation
- neuron sprout neurites that have growth cones on their tips which direct the neurite to its target location
- A dendritic filopodium contacts an axon
- Leads to recruitment of synaptic vesicles and active zone proteins to the presynaptic membrane
- Neurotransmitter receptors accumulate post-synaptically
central synapse vs. peripheral synapse
- CNS has mostly axon-dendrite synapses
- PNS has mostly neuro-muscular synapse
• neuromuscular junction has no post-synaptic
membrane in the form of a dendrite but in the
form of a motor endplate
• In the motor endplate many junctional fold with
numerous neurotransmitter receptors (AcHr) can
be found - Differences between CNS and PNS synapses:
• CNS synapses have no basal lamina
• CNS synapses have no junctional folds but have
dendritic spines
• Different neurotransmitters and different receptors:
Central synapses –>excitatory: glutamate
Peripheral synapses –>excitatory: Ach
early LTP
- LTP without protein synthesis:
1. AMPA receptor binds glutamate and glycine opening
the sodium pore
2. Depolarisation: NMDA receptor lose its
magnesium block opening the calcium pore
3. Calcium influx: more AMPA receptors (with increased
glutamate affinity) to be placed on the post-synaptic
membrane
• The increase in Ca2+ activates several
downstream signalling pathways, including
calcium/calmodulin-dependent protein kinase II
(CaMKII), protein kinase C (PKC), and tyrosine
kinases
4. The post-synaptic neuron releases retrograde
messenger molecules like NO and arachidonic acid to
initiate larger glutamate release from the pre-synaptic
membrane
late LTP
- Late LTP: formation of new synapse
1. With repeated tetani the calcium influx also recruits
an adenylyl cyclase
2. This generates cAMP which activates PKA
3. This leads to the activation of MAP kinase
4. MAP kinase translocates to the nucleus where it
phosphorylates CREB-1
5. CREB-1 in turn activates transcription genes that lead
to synapse formation
functional brain area development
The brain areas undergo overproduction of synapses at different times followed by synaptic pruning in order to keep the most functional synapses and get rid of dysfunctional:
- month 3/4 post-natal: visual and auditory cortex
- month 8/9: language (angular gyrus/Broca’s area)
- 1/2 years: cognitive areas (prefrontal cortex)
adult neurogenesis
Adult neurogenesis starts with the proliferation of neural stem cells in 2 distinct hippocampus areas:
• The sub-granular zone (SGZ), part of the dentate
gyrus of the hippocampus where neural stem cells
give birth to granule cells (implicated in memory
formation and learning)
• The subventricular zone (SVZ) of the lateral ventricles.
Neural stem cells migrate to the olfactory bulb where
they differentiate into interneurons participating in the
sense of smell. In humans, however, few if any
olfactory bulb neurons are generated after birth
