Potentiation of Tonic Gabaergic Inhibition by Activation of Postsynaptic Kainate Receptors

Authors

L Jiang, Department of Neurobiology and Behavior/Center for Nervous Systems Disorders Research, Stony Brook University, Stony Brook, New York 11794, USA.
D Kang, Park Ridge High School, 2 Park Avenue, Park Ridge, NJ 07656, USA.
J Kang, Department of Cell Biology and Anatomy, New York Medical College, 15 Dana Road, Valhalla, NY 10595, USA. Electronic address: jian_kang@NYMC.edu.

Author Type(s)

Faculty

DOI

10.1016/j.neuroscience.2015.04.043

Journal Title

Neuroscience

First Page

448

Last Page

54

Document Type

Article

Publication Date

7-9-2015

Abstract

Presynaptic kainate-type glutamate ionotropic receptors (KARs) that mediate either the depression or the facilitation of GABA release have been intensively studied. Little attention has been given to the modulation of GABAA receptors (GABAARs) by postsynaptic KARs. Recent studies suggest that two GABAAR populations, synaptic (sGABAAR) and extrasynaptic (eGABAAR) GABAARs, mediate phasic and tonic forms of inhibition, respectively. Tonic inhibition plays an important role in the excitability of neuronal circuits and the occurrence of epileptic seizures. For this study, we are the first to report that the activation of postsynaptic KARs by the KAR agonist, Kainic acid (KA, 5 μM), enhanced tonic inhibition by potentiating eGABAARs. KA enhanced THIP-induced eGABAAR currents and prolonged the rise and decay time of muscimol-induced sGABAAR/eGABAAR currents, but also depressed the amplitude of evoked inhibitory postsynaptic currents (IPSCs), unitary IPSCs (uIPSCs), and muscimol-induced sGABAAR/eGABAAR currents. The PKC inhibitor, staurosporine (1 μM), in the patch pipette solution fully blocked the KA-induced potentiation of tonic inhibition, suggesting the involvement of an intracellular PKC pathway. Our study suggests that the activation of postsynaptic KARs potentiates eGABAARs but depresses sGABAARs. By activating postsynaptic KARs, synaptically released glutamate depresses phasic inhibition to facilitate neuronal plasticity, but potentiates tonic inhibition to protect neurons from over-excitation.

Recommended Citation

Jiang, L., Kang, D., & Kang, J. (2015). Potentiation of Tonic Gabaergic Inhibition by Activation of Postsynaptic Kainate Receptors. Neuroscience, 298, 448-54. https://doi.org/10.1016/j.neuroscience.2015.04.043