Synaptic Transmission from Somatostatin-expressing Interneurons to Excitatory Neurons Mediated by α5-subunit-containing GABAA Receptors in the Developing Visual Cortex

Abstract

Dendrite-targeting somatostatin-expressing interneurons (SST-INs) powerfully control signal integration and synaptic plasticity in pyramidal dendrites during cortical development. We previously showed that synaptic transmission from SST-INs to pyramidal cells (PCs) (SST-IN → PC) in the mouse visual cortex suddenly declined at around the second postnatal week. However, it is unclear what specific postsynaptic mechanisms underlie this developmental change. Using multiple whole-cell patch-clamp recordings, we found that application of an α5-GABA_A receptor-selective inverse agonist, alpha5IA, significantly weakened SST-IN → PC unitary inhibitory postsynaptic currents (uIPSCs) in layer 2/3 of the mouse visual cortex, but had no effect on uIPSCs from SST-INs to other types of interneurons. The extent of alpha5IA-induced reduction of SST-IN → PC synaptic transmission was significantly larger at postnatal days 11-13 (P11-13) than P14-17. Moreover, α5-subunit-containing GABA_A receptors (α5-GABA_ARs)-mediated uIPSCs had slow rise and decay kinetics. Apart from pharmacological test, we observed that SST-IN → PC synapses did indeed contain α5-GABA_ARs by immunogold labeling for electron microscopy. More importantly, coinciding with the weakening of SST-IN → PC synaptic transmission, the number of α5-GABA_AR particles in SST-IN → PC synapses significantly decreased at around the second postnatal week. Together, these data indicate that α5-GABA_ARs are involved in synaptic transmission from SST-INs to PCs in the neocortex, and are significantly diminished around the second postnatal week.

Keywords: pyramidal cells; somatostatin-expressing interneurons; synaptic transmission; visual cortex; α5-GABA(A)Rs.