Bidirectional plasticity of GABAergic tonic inhibition in hippocampal somatostatin- and parvalbumin-containing interneurons

Abstract

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GABAA receptors present in extrasynaptic areas mediate tonic inhibition in hippocampal neurons regulating the performance of neural networks. In this study, we investigated the effect of NMDA-induced plasticity on tonic inhibition in somatostatin- and parvalbumin-containing interneurons. Using pharmacological methods and transgenic mice (SST-Cre/PV-Cre x Ai14), we induced the plasticity of GABAergic transmission in somatostatin- and parvalbumin-containing interneurons by a brief (3 min) application of NMDA. In the whole-cell patch-clamp configuration, we measured tonic currents enhanced by specific agonists (etomidate or gaboxadol). Furthermore, in both the control and NMDA-treated groups, we examined to what extent these changes depend on the regulation of distinct subtypes of GABAA receptors. Tonic conductance in the somatostatin-containing (SST+) interneurons is enhanced after NMDA application, and the observed effect is associated with an increased content of α5-containing GABAARs. Both fast-spiking and non–fast-spiking parvalbumin-positive (PV+) cells showed a reduction of tonic inhibition after plasticity induction. This effect was accompanied in both PV+ interneuron types by a strongly reduced proportion of δ-subunit-containing GABAARs and a relatively small increase in currents mediated by α5-containing GABAARs. Both somatostatin- and parvalbumin-containing interneurons show cell type-dependent and opposite sign plasticity of tonic inhibition. The underlying mechanisms depend on the cell-specific balance of plastic changes in the contents of α5 and δ subunit-containing GABAARs.

Keywords

• GABA
• tonic inhibition
• hippocampus
• interneurons
• plasticity
• extrasynaptic receptors