Changes in Dendritic and Synaptic Function During Early Postnatal Development of the Mouse Barrel Cortex

Abstract

Neuronal dendrites are the main recipients of glutamatergic synaptic input and participate in active integration of information via the generation of local, regenerative events called dendritic spikes. Whilst these regenerative events have been mostly characterised in adult cortical and hippocampal neurons, it is unclear whether dendritic spikes require mature, fully established synapses or whether they can occur early during development. To explore this possibility, focal synaptic stimulation was used to induce dendritic spiking in postnatal day 7-20 spiny stellate neurons of the layer 4 barrel cortex. However, no nonlinearity characteristic of dendritic spiking was observed in these young neurons, suggesting dendritic spikes are a feature of mature synapses.
During the first 3 postnatal weeks, functional and structural synaptic formation and maturation is accompanied by several changes in the morphology and protein content of postsynaptic spines. Correct function of synaptic transmission relies on the precise apposition between pre- and post-synaptic compartments. Synaptic components, such as ion channels, adhesion proteins and neurotransmitter receptors, are recruited to the post-synaptic sites to establish synaptic function. In excitatory synapses, these proteins are spatially organized and held in place in the spines by members of the membrane-associated guanylate kinase family of proteins. Two members of this family, PSD95 and SAP102, have been identified as major players of synaptic maturation and receptor trafficking, respectively. Developmental profiling of these two proteins revealed a layer-specific, developmentally regulated pattern of expression. Both proteins are highly enriched from P4 in L1 and L4, while the protein levels in L2/3 increase sharply over time. L5A is enriched with PSD95, but not SAP102, from the earliest age and this layer receives inputs from Cplx3-positive subplate neurons.

Date of Award	23 Jan 2020
Original language	English
Awarding Institution	The University of Bristol
Supervisor	Michael C Ashby (Supervisor)