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

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

doi:10.3389/fncel.2021.718413

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 GABAB receptors (GABABRs), 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 GABABRs 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.

Highlights

The mammalian cortex is a conspicuously layered structure that receives inputs from afferent subcortical and other cortical areas in a layer-specific manner (Douglas and Martin, 2004)
We systematically mapped the relationship between action potential (AP) output to input currents during combined current injections into the soma and apical dendrite of thick-tufted L5b pyramidal neurons in rat (P28–40) somatosensory cortex using dual patch-clamp recordings
Post hoc tests revealed that baclofen significantly reduced synergy in the presence of nimodipine. These results indicated that inhibition of Ca2+ spikes does not reduce apical amplification of AP output, at least on the time scale employed here for the Partial Information Decomposition (PID) analysis of the AP rate. These results demonstrated that direct inhibition of L-type Ca2+-channels by dendritic GABAB receptors (GABABRs) plays only a minor role in shaping the overall F-I relationship and strongly suggested that other mechanisms mediate the decrease in the apical amplification of AP output after dendritic GABABR activation

Summary

INTRODUCTION

The mammalian cortex is a conspicuously layered structure that receives inputs from afferent subcortical and other cortical areas in a layer-specific manner (Douglas and Martin, 2004). It was shown that coupling between the apical and basal compartments mainly depends on cholinergic and metabotropic glutamate receptor activation in awake mice, but may be independent of L-type Ca2+Channels (Suzuki and Larkum, 2020). This suggests that other cellintrinsic voltage-dependent mechanisms may contribute to the synergistic interaction between depolarization in the dendritic and perisomatic compartments. We systematically mapped the effect of combined current injections into the soma and apical dendrite and used PID to elucidate the mechanisms underlying dendro-somatic synergy and its regulation by GABABR-activated effector pathways

MATERIALS AND METHODS

RESULTS

DISCUSSION

CONCLUSION

ETHICS STATEMENT