GABA B Receptor-Mediated Regulation of Dendro-Somatic Synergy in Layer 5 Pyramidal Neurons

Jan M Schulz; Jim W Kay; Josef Bischofberger; Matthew E Larkum

doi:10.3389/fncel.2021.718413

GABA _B Receptor-Mediated Regulation of Dendro-Somatic Synergy in Layer 5 Pyramidal Neurons

Front Cell Neurosci. 2021 Aug 25:15:718413. doi: 10.3389/fncel.2021.718413. eCollection 2021.

Authors

Jan M Schulz¹, Jim W Kay², Josef Bischofberger¹, Matthew E Larkum³

Affiliations

¹ Department of Biomedicine, University of Basel, Basel, Switzerland.
² Department of Statistics, University of Glasgow, Glasgow, United Kingdom.
³ Institute for Biology, Humboldt-Universität zu Berlin, Berlin, Germany.

Abstract

Synergistic interactions between independent synaptic input streams may fundamentally change the action potential (AP) output. Using partial information decomposition, we demonstrate here a substantial contribution of synergy between somatic and apical dendritic inputs to the information in the AP output of L5b pyramidal neurons. Activation of dendritic GABA _B receptors (GABA _B Rs), known to decrease APs in vivo, potently decreased synergy and increased somatic control of AP output. Synergy was the result of the voltage-dependence of the transfer resistance between dendrite and soma, which showed a two-fold increase per 28.7 mV dendritic depolarization. GIRK channels activated by dendritic GABA _B Rs decreased voltage-dependent transfer resistances and AP output. In contrast, inhibition of dendritic L-type Ca²⁺ channels prevented high-frequency bursts of APs, but did not affect dendro-somatic synergy. Finally, we show that NDNF-positive neurogliaform cells effectively control somatic AP via synaptic activation of dendritic GIRK channels. These results uncover a novel inhibitory mechanism that powerfully gates cellular information flow in the cortex.

Keywords: GIRK channels; HCN channels – h current; L-type calcium channels; dendrite; interhemispheric inhibition; interneuron; neocortex; neurogliaform cells.