# The gephyrin scaffold modulates cortical layer 2/3 pyramidal neuron responsiveness to single whisker stimulation

## TL;DR

This study shows how changes in a brain protein called gephyrin affect how neurons in the mouse brain respond to sensory input.

## Contribution

The study reveals how specific modifications to gephyrin influence neuronal activity and GABA receptor selection in sensory processing.

## Key findings

- Gephyrin post-translational modifications differentially modulate L2/3 pyramidal neuron activity during whisker stimulation.
- Gephyrin PTMs influence the size of the neuronal population responding to sensory input.
- Gephyrin PTMs preferentially select synaptic GABAA receptor subunits.

## Abstract

Gephyrin is the main scaffolding protein at inhibitory postsynaptic sites, and its clusters are the signaling hubs where several molecular pathways converge. Post-translational modifications (PTMs) of gephyrin alter GABAA receptor clustering at the synapse, but it is unclear how this affects neuronal activity at the circuit level. We assessed the contribution of gephyrin PTMs to microcircuit activity in the mouse barrel cortex by slice electrophysiology and in vivo two-photon calcium imaging of layer 2/3 (L2/3) pyramidal cells during single-whisker stimulation. Our results suggest that, depending on the type of gephyrin PTM, the neuronal activities of L2/3 pyramidal neurons can be differentially modulated, leading to changes in the size of the neuronal population responding to the single-whisker stimulation. Furthermore, we show that gephyrin PTMs have their preference for selecting synaptic GABAA receptor subunits. Our results identify an important role of gephyrin and GABAergic postsynaptic sites for cortical microcircuit function during sensory stimulation.