Tonically Active α5GABAA Receptors Reduce Motoneuron Excitability and Decrease the Monosynaptic Reflex.

Martha Canto-Bustos,David Elias-Viñas,Carlos A Cuellar,Ricardo Felix,Paulina Osuna,Elías Manjarrez,Vinicio Granados-Soto,Rodolfo Delgado-Lezama,Emanuel Loeza-Alcocer

doi:10.3389/fncel.2017.00283

Abstract

Motoneurons, the final common path of the Central Nervous System (CNS), are under a complex control of its excitability in order to precisely translate the interneuronal pattern of activity into skeletal muscle contraction and relaxation. To fulfill this relevant function, motoneurons are provided with a vast repertoire of receptors and channels, including the extrasynaptic GABAA receptors which have been poorly investigated. Here, we confirmed that extrasynaptic α5 subunit-containing GABAA receptors localize with choline acetyltransferase (ChAT) positive cells, suggesting that these receptors are expressed in turtle motoneurons as previously reported in rodents. In these cells, α5GABAA receptors are activated by ambient GABA, producing a tonic shunt that reduces motoneurons’ membrane resistance and affects their action potential firing properties. In addition, α5GABAA receptors shunted the synaptic excitatory inputs depressing the monosynaptic reflex (MSR) induced by activation of primary afferents. Therefore, our results suggest that α5GABAA receptors may play a relevant physiological role in motor control.

Highlights

Extrasynaptic GABAA receptors play important roles in supra-spinal nuclei of the Central Nervous System (CNS) regulating neuron excitability and network activity by tonically inhibiting and shunting mature neuronal membranes, which set the threshold for action potential generation and temporal window for synaptic integration (Farrant and Nusser, 2005; Wlodarczyk et al, 2013)
We found that motoneurons presented a tonic current mediated by high affinity α5 subunit-containing GABAA (α5GABAA) Receptors Tonically Inhibit Motoneurons
In the present report we show that the α5GABAA receptors tonically activated by ambient GABA produce a tonic inhibitory current that modulates the passive and active properties of the turtle spinal motoneurons

Summary

INTRODUCTION

Extrasynaptic GABAA receptors play important roles in supra-spinal nuclei of the Central Nervous System (CNS) regulating neuron excitability and network activity by tonically inhibiting and shunting mature neuronal membranes, which set the threshold for action potential generation and temporal window for synaptic integration (Farrant and Nusser, 2005; Wlodarczyk et al, 2013). These receptors are conformed mainly by α4, α5 and α6 subunits, sometimes they may contain α2 and α3 subunits (Farrant and Nusser, 2005). Here we show that α5GABAA receptors depress the MSR

MATERIALS AND METHODS

RESULTS

DISCUSSION