Abstract

A tonic form of synaptic inhibition occurs in discrete regions of the central nervous system and has an important role in controlling neuronal excitability. Recently, we reported that GABA present in astrocyte is the major source of tonic inhibition in cerebellum and that GABA is released through Bestrophin-1 channel by direct permeation. In this study, we screened for the presence of astrocytic GABA in various brain regions such as hippocampus, thalamus, hypothalamus and cerebellum using immunohistochemistry. We found that astrocytic GABA was present in the regions that were reported to show tonic inhibition. Because the existence of tonic inhibition in hippocampal CA1 is somewhat controversial, we compared the amount of astrocytic GABA and tonic inhibition between the hippocampal CA1 pyramidal cell layer and the cerebellar granule cell layer. Unlike cerebellar glial cells, hippocampal astrocytes did not contain GABA. The tonic inhibition was also much lower in the pyramidal neurons of hippocampal CA1 compared to the granule cells of cerebellum. Nevertheless, most of the hippocampal astrocytes expressed Bestrophin-1 channel. These data indicate that the absence of astrocytic GABA results in a low level of tonic inhibition in hippocampal CA1 region.

Highlights

  • Tonic inhibition originates from the sustained activation of high affinity gamma-aminobutyric acid (GABA) receptors by ambient GABA [1]

  • We recently reported that Ca2+-activated anion channel, Bestrophin 1 (Best1), mediates tonic inhibition by releasing tonic GABA from glia

  • We demonstrated that GABA directly permeates through Best1 and that tonic inhibition is eliminated by silencing Best1

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Summary

Introduction

Tonic inhibition originates from the sustained activation of high affinity gamma-aminobutyric acid (GABA) receptors by ambient GABA [1]. Other investigators reported tonic inhibition currents in pyramidal neuron after pre-incubating with GABA-transaminase inhibitor or GABA [3,14] to artificially enhance the ambient GABA level. These studies indicated that pyramidal neurons express high affinity extrasynaptic GABA receptors, ready to sense tonic GABA release. Significant tonic inhibition was found in the interneurons of hippocampal CA1 region [16]. The existence of tonic inhibition and source of GABA release in hippocampal CA1 region are still in question

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