Robust perisomatic GABAergic self-innervation inhibits basket cells in the human and mouse supragranular neocortex.

Viktor Szegedi,Judith Baka,Gábor Molnár,Karri Lamsa,Melinda Paizs,Pál Barzó,Gabor Tamas

doi:10.7554/elife.51691

Abstract

Inhibitory autapses are self-innervating synaptic connections in GABAergic interneurons in the brain. Autapses in neocortical layers have not been systematically investigated, and their function in different mammalian species and specific interneuron types is poorly known. We investigated GABAergic parvalbumin-expressing basket cells (pvBCs) in layer 2/3 (L2/3) in human neocortical tissue resected in deep-brain surgery, and in mice as control. Most pvBCs showed robust GABAAR-mediated self-innervation in both species, but autapses were rare in nonfast-spiking GABAergic interneurons. Light- and electron microscopy analyses revealed pvBC axons innervating their own soma and proximal dendrites. GABAergic self-inhibition conductance was similar in human and mouse pvBCs and comparable to that of synapses from pvBCs to other L2/3 neurons. Autaptic conductance prolonged somatic inhibition in pvBCs after a spike and inhibited repetitive firing. Perisomatic autaptic inhibition is common in both human and mouse pvBCs of supragranular neocortex, where they efficiently control discharge of the pvBCs.

Highlights

Autapses are synapses made by a neuron onto itself (Bekkers, 2003; Deleuze et al, 2014)
Studies on experimental animals have reported autaptic self-innervation in some inhibitory as well as in excitatory neurons in the brain, (Karabelas and Purpura, 1980; Lubke et al, 1996; Thomson et al, 1996; Cobb et al, 1997; Pouzat and Marty, 1998; Bacci et al, 2003; Connelly and Lees, 2010; Karayannis et al, 2010; Jiang et al, 2015; Yin et al, 2018), little is known about autapses in human nerve cells, and only a single study has investigated the operation of autaptic self-inhibition in the human neocortex (Jiang et al, 2012)
We show that GABAAR-mediated inhibition is present in most parvalbumin-expressing basket cells (pvBCs) in both species and that perisomatic autaptic contacts in these interneurons suppress excitability and inhibit repetitive firing

Summary

Introduction

Autapses are synapses made by a neuron onto itself (Bekkers, 2003; Deleuze et al, 2014). Studies on experimental animals have reported autaptic self-innervation in some inhibitory as well as in excitatory neurons in the brain, (Karabelas and Purpura, 1980; Lubke et al, 1996; Thomson et al, 1996; Cobb et al, 1997; Pouzat and Marty, 1998; Bacci et al, 2003; Connelly and Lees, 2010; Karayannis et al, 2010; Jiang et al, 2015; Yin et al, 2018), little is known about autapses in human nerve cells, and only a single study has investigated the operation of autaptic self-inhibition in the human neocortex (Jiang et al, 2012). Evidence for autapses exists in the human epileptic infragranular neocortex, where high-frequency spike bursts are associated with autaptic GABA

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