Neurobio Exam 3- Wiring the brain

3 stages of neurogenesis

birth, migration, differentiation

Birth location

occurs at ventricular surface, ventricular and marginal zone

Ventricular zone

contains neural progentior cells and radial glial cells

Radial glial cells

develop spinal cord

Neurogenesis steps

radial glial cells extend to reach pia at surface of brain, interkinetic nuclear migration, radial glial cells retract arms, cell division, migration

Interkinetic nuclear migration

nucelus migrates away and back toward ventricular zone, necessary for DNA replication and cell division

Asymmetrical cell division

1 neuroblast, 1 radial glial cell/proginetor, maintains progenitor pool, later in development

Symmetrical cell divison

2 radial glial cells/progentiors, early in development

Schematic development of primate embryonic neocortex

marginal zone, cortical plate, subventricular zone, intermediate zone

Neuroblasts

won’t divide again

Cortical migration

neuroblasts move from ventricular surface to dorsal aspect using radial glial cells as a path, distinct morphology, cortex assembles inside out (layer 6 to 1)

Subplate

made from the first cells that migrate, important for early motor behavior, excitatory

Reelin

protein that binds to low density lipoprotein receptors, stop sign

Tangential migration

neuroblasts migrate in streams from ventricular zone of ventral procencephalon to cortex without a path, gives rise to inhibitory interneurons and oligosacchrides

Ganglionic eminence

tangential migration, creates inhibitory interneurons, medial and caudal go to cortex, lateral goes to olafactory bulb

Neuronal differentiation

occurs immediately after migration, shape change, layers differentiate before other layers migrate

Adult neurogenesis discovery

discovered with radioactive thymidine

3 hypothesis of cortical differentiation

radial unit hypothesis, transcriptional landscapes, input dependent programming

Radial unit hypothesis

progenitor cells give rise to columns, cortical protomap exists in ventricular zone

Transcriptional patterning

neurons in discrete cortical regions have transcriptional profiles

Anterior transcriptional factor

Pax6, mutant expands visual and reduces somatosensory and motor

Posterior transcriptional factor

Emx2, mutant expands motor and reduces visual and somatosensory

Input dependent programming

input necessary for critical development

Cortical transplants

need transplant before fibers reach that area

Axon adhesion

promotes outgrowth, uses CAMs

Fasciculation

later extending axons use pioneer axons

CAMs

diverse, homotypic or heterotypic interaction

LICAM

inactivation causes abnormal muscle innervation, axons sprout from nerve

NCAM

loss causes abnormal retinal axon pathfinding

Cadherins

regulate axon fasciculation, interacts with actin to reguate outgrowth

pcdhl7 (cadherin)

important for homotypic fasciculation of amygdala axons

Synaptogenesis

pre and post synaptic specilization form at sites of active contact, dendritic filiopodium contacts axons, synaptic vesicles and active zone proteins recruited

NMJ formation

motor neuron secretes agrin into basal lamina, MuSK/agrin receptor on muscle receives signal, MuSK activates Rapsyn, Rapsyn cluster Ach receptors into plaque

Neurexin (type of CAM)

presynaptic, 3 genes, mutliple isoforms

Neuroligin (type of CAM)

post synaptic, 4 genes, multiple isoforms

3 effects of neurexin deletion

decrease presynaptic calcium, presynaptic release probability, and synapse number

Neuroligin cell type targets

1-excitatory, 2- inhibitory, 3- excitatory and inhibitory, 4- glycoinergic

Neurexin mutations

linked to schizophrenia, tourettes, eplipepsy, autism

Neuroligin 3 and 4 mutations

linked to autism

Synaptic refinement

requires synpatic pruning

4 types of synaptic refinement

synaptic capacity, rearrangment, segregation, programmed cell death

Synaptic capacity

how many targets an axon innervates

Synaptic rearrangement

changes in how many synapses individual input neurons have on recieving neurons

Synaptic segregation

change in which neurons an axon will synapse on

Excitatory synapse transmission

receptors can be metabotropic or ionotropic

Ionotropic glutamate receptors

AMPA and NMDA

Critical periods

large scale changes can be made

Critical period ending hypothesis

plasticity diminishes when axon growth stops or synaptic transmission matures