Medicine Notes Neuroscience 1 Notes
Contains notes for the neuroscience module covered in Michaelmas Term...
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Discuss the role for migration in the development of the central nervous system. How can disruption of migration result in developmental disorders?
Intro
Migration of cells during development of CNS plays a key role in the formation of a functional CNS
This is because correct spatial location of neurons ensure accurate synaptic contact with neighbouring and more distant neurons
Mutations in the migratory process results in severe CNS disorders
Cerebral cortex
Grey matter of cerebral cortex consists of 6 neuronal layers each with a specific function
Layer 4 receives input from the thalamus
Layer 5 projects to subcortical areas
Within the cortex there are both excitatory glutamatergic and inhibitory GABAergic neurons- both of these classes of neurons arise from different areas of CNS and migrate by different routes
Excitatory glutamatergic
Originate from the radial glial cells of the CNS – these cells are multipotent and have processes that attach to both the pia mater and to the ventricular surface
On receiving neurogenic signals these cells undergo asymmetric division to give rise to a neuronal progenitor and another radial glia cell
To show the proliferative capacity of these cells phosphohistone labelling was done and this showed a layer of dividing cells in the ventricular zone. This labelling technique also showed the presence of two additional layers which contained dividing cells: subventricular and outersubventricular layers and these contain the intermediate progenitors of the radial glia
These cells also give rise to cortical neurons and their importance is shown in Tbr2 KO models which often resulted in microcephaly in mouse models
Once the excitatory neuronal progenitor is formed migration towards the pia mater occurs
During the early stages of corticogenesis radial independent translocation occurs
In this process a large radial process of the neuronal progenitor which either emerges just before migration or is inherited from the radial glia cells attaches to the pial surface
Once this occurs the process of the neuronal progenitor attached to the ventricular surface detaches
This is then followed by cytoskeletal arrangements of actin in the leading process of the neuronal progenitor which causes the leading process to contract and pull the somal body towards the pia
To show that this occurs live imaging studies of corticogenesis has been done and it has been shown that during the early stages neuronal progenitors rapidly migrate to the surface in a fluid like motion
During the later stages of corticogenesis radial migration proceeds by radial dependent dependent locomotion and relies on the radial glia to act as a scaffold for the migrating neuronral progenitors
Neurons undergoing this form of migration have free leading processes
Once these cells have been detatched from the ventricular surface, polymerisation of actin in the leading process causes it to extend towards the pia
Importance of cytoskeletal rearrangements have been shown in filamin-1 KO models in mice which lead to periventricular heterotopia
After the leading process has extended the neuronal progenitor makes transitatory connections with the radial glia. These interactions involve integrin receptors and ligands
Specific KO of either of these leads to severe migratory defects
Once adhesion...
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Contains notes for the neuroscience module covered in Michaelmas Term...
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