Post natal brain development

Question 1

Synapse formation

Answer 1

First contact is mediated by recognition of cell adhesion molecules on the membrane

Nectins, ephrins and cadherins form temporary connections between pre-and postsynaptic partners - immature synapse

Question 2

How are synapses formed at specific locations

Answer 2

Chemo-affinity hypothesis:
Matching of moelcular markers on axons and dendrites defines synapse sepcificity

Guidance molecules: ephrins and + eph
Adhesion molecules: caherins and protocadherins

Question 3

Protocadherins

Answer 3

Molecular codes for synapse specificity
Different protocadherin isoforms expressed at the same synapses.
Different synaptic sites have different complements of adhesion molec.

Question 4

Dscam

Answer 4

Study in drosophilias
Dscams are repulsive guidance cues that control non-matching rather than matching
Mammalian protocadherins are more complex

Question 5

Synapse maturation

Answer 5

Regulated by different set of cell adhesion molecules
Gene mutations - disturbed synapse maturation - altered wiring of networks

Inductive factors
-SynCAM
-EphrinB/EphBR
-Neurexin
-Neuroligin
-Neuregulin 1

Question 6

Induction of synapse maturation

Answer 6

Adhesion molecules provide:
stability
Clustering of pre- and postsynaptic proteins involved in neurotransmission

Changes in DNA sequence of adhesion molecules associated with autism and schizophrenia

Question 7

Neuroligin

Answer 7

Sufficient to induce presynaptic maturation
Expression of neuroligin in non-neuronal cell (HEK-293)
These cells have no synaptic specifications

Question 8

Maturation accompaniment

Answer 8

Accompanied by changes in spine shape, size and number
Measured by morphology (size and shape)
Physiology - electrophysiological properties, such as glutamatergic receptors

Immature synapses characterized by long filopodia like processes and they lack a spine head.
Maturation: spine becomes shorter and forms a spine head
Mushroom and cup shaped spines are the most stable spines.
Maturation is observed in cultured neurons.
Fragile X syndrome: many immature spines and much fewer mature spines.

Question 9

Synapse elimination

Answer 9

Too many synaptic connections are formed - requires refinement
Competition for innervation - winner remains, losers retract

Neuromuscular junction polyneuronal innervation: target muscle cell innervated by multiple neurons
Competition determines which input remains
Inputs lost, retract until only 1 input remains

Question 10

Neurotrophin recepetors

Answer 10

TrkA = NGF
TrkB - BDNF NT-4/5
TrkC = NT-3

Secreted by target cells
competition for availability

Lead to axon growth and retraction
Synapse maturation/elimination
Neuronal survivial

Question 11

Nerve cell elimination

Answer 11

Loss of synaptic connections in instructive for neuronal survival.
During development there is an overproduction of synapses, destroying those that are unnecessary ensures that important neuronal circuits are efficient and are specialized for their specific tasks

Question 12

Experience dependent plasticity

Answer 12

synchronized activity of pre and post synaptic cell strengthens the connection between them. (Hebb’s postulate)
Correlated patter of action potentials determines which synapses persist and strengthen.
Synapses with neurons that do not fire together will be eliminated

Question 13

Synapse elimination in the visual cortex

Answer 13

Synapse elimination is accompanied by reduction in grey matter volume
Timing varies per brain region depending on critical period.
Usually happens in early and late childhood
childhood.
Most evidence derived from visual cortex.
First: increase in synapse number.
Between 1 and ~10 years: sharp decrease.
Then plateau and later reduction as a result of aging.
Synapse elimination during childhood: refinement of neural circuitry

Question 14

Synapse elimination and critical period

Answer 14

Coincides with critical period of cortical regions
The visual cortex is the most well-studied example

Question 15

Occular dominance

Answer 15

Occular dominance columns in the visual cortex
Tracer injection in eye stains cortical areas that receive inputs from this eye.
Also develop postnatal
Receptive field = occular dominance column = amount of input that neuron in the visual cortex recieves from left and right eye

Question 16

Monocular deprivation

Answer 16

Receptive fields of open eye enlarge
Closed eye: severely reduced or even absent

Question 17

Occular dominance plasticity

Answer 17

Most plastic during early development period when visual input shapes neural connections.

Column 1 - Contralateral eye
Column 7 - ipsilateral eye

Normal distribution - closure of one eye during the critical period shifts responses completely to the non-deprived eye
No effect in adult, after critical period
Lazy eye: shift towards non-lazy eye

Question 18

ECM and occular dominance

Answer 18

Limits ocular dominance plasticity
PNNs - increase in number of PNNS during postnatal development - brain becomes less plastic
PNN density peaks at the end of critical period in visual cortex

Degradation of the ECM restores ocular dominance plasticity in adult cortex

Question 19

Activity dependent modulation of the ECM

Answer 19

1)Activity dependent release and/or activation of ECM degrading enzymes
2)Local degradation of the ECM
3) Increased lateral diffusion of receptors
4)ECM signalling via integrins

Question 20

Infantile amnesia

Answer 20

Early 0-3 years episodic memories are rapidly forgotten
Episodic memory = who, what, where and when

Animals also show infantile amnesia

Question 21

Amygdala

Answer 21

ECM protects against memory erasure.

Question 22

Critical period of the hippocampus : postnatal neurogenesis

Answer 22

Infantile amnesia
Neurogenesis in subgranular zone remains high during first post natal years but declines during childhood.
This declines in mice after 3 years