Michael

Question 1

Define the critical period

What drives change during this period?

Answer 1

A breif period of time during very early development where you get robust LTP, it is largely dependent on experience

Question 2

What changes in protein expression facilitate faster transmission during development?

And what drives these changes?

Answer 2

• Change from kainate to AMPAR in synapses (AMPAR is faster)
• Increase in GluN2A/2B ratio (2A is faster)
• Insertion of AMPAR into NMDA only synapses
• Increase in P/Q-type channels (more likely to release NT)
• Switch from GluA4 to GluA2 (PKA drives insertion of GluA4)

Experience and neuronal activity drives these changes

Question 3

How does synaptic plasticity shape connectivity during development?

Answer 3

LTP leads to an increase in thalamocortical connectivity
In early development axons send out branches to other cells and contact is temporary UNLESS there is LTP to strengthen the synapse- swtich from slow EPSP at that synapse to fast LTP

Question 4

How do action potential firing patterns change throughout development?

Answer 4

Switch from broad temporal summation to precise action potential timing (in thalamus)
In hippocampus there is a switch from GDP to independent firing, the disengagement is mediated by GABAergic inhibition

Spontaneous synchronised firing keeps cells alive preventing apoptosis until they are needed later in development

Question 5

How does GABA mediate tonic and phasic signalling in early development via non-canonical release?

Answer 5

GABA is the main excitatory NT in the first week of life, and mediates giant depolarising potentials in which neurons all fire together at the same time
It mediates large and very long currents in early development until the disengagement from synchronous firing

The GABAR subunits have very slow kinetics in early development

Question 6

What factors lead to an increase in synaptic inhibition during brain development?

Answer 6

GABAaR becomes inhibitory due to the insertion of KCC2 into the membrane, which lets Cl- ions out of the cell so the Cl- gradient is now into the cell
Increase in thalamocortical neuron connections onto inhibitory neurons during development

Question 7

How is synaptic development altered in neurodevelopmental disorders?

Answer 7

• critical period is delayed in fragile X mice
• delay in GABA becoming inhibitory
• premature faster NMDAs in SAP102 KO mice, and prevents experience dependent connectivity
• premature increases in connectivity in Valproate model of ASD