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Public Library of Science, PLoS ONE, 4(10), p. e0124765, 2015

DOI: 10.1371/journal.pone.0124765

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The GLP-1 Receptor Agonist Exendin-4 and Diazepam Differentially Regulate GABAA Receptor-Mediated Tonic Currents in Rat Hippocampal CA3 Pyramidal Neurons

Journal article published in 2015 by Sergiy V. Korol ORCID, Zhe Jin ORCID, Bryndis Birnir
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Glucagon-like peptide-1 (GLP-1) is a metabolic hormone that is secreted in a glucose-dependent manner and enhances insulin secretion. GLP-1 receptors are also found in the brain where their signalling affects neuronal activity. We have previously shown that the GLP-1 receptor agonists, GLP-1 and exendin-4 enhanced GABA-activated synaptic and tonic currents in rat hippocampal CA3 pyramidal neurons. The hippocampus is the centre for memory and learning and is important for cognition. Here we examined if exendin-4 similarly enhanced the GABA-activated currents in the presence of the benzodiazepine diaze-pam. In whole-cell recordings in rat brain slices, diazepam (1 μM), an allosteric positive modulator of GABA A receptors, alone enhanced the spontaneous inhibitory postsynaptic current (sIPSC) amplitude and frequency by a factor of 1.3 and 1.6, respectively, and doubled the tonic GABA A current normally recorded in the CA3 pyramidal cells. Importantly, in the presence of exendin-4 (10 nM) plus diazepam (1 μM), only the tonic but not the sIPSC currents transiently increased as compared to currents recorded in the presence of diaze-pam alone. The results suggest that exendin-4 potentiates a subpopulation of extrasynaptic GABA A receptors in the CA3 pyramidal neurons.