Regulation of GABAergic inputs to CA1 pyramidal neurons by nicotinic receptors and kynurenic acid.

The Journal of Pharmacology and Experimental Therapeutics
Jyotirmoy BanerjeeEdson X Albuquerque

Abstract

Impaired α7 nicotinic acetylcholine receptor (nAChR) function and GABAergic transmission in the hippocampus and elevated brain levels of kynurenic acid (KYNA), an astrocyte-derived metabolite of the kynurenine pathway, are key features of schizophrenia. KYNA acts as a noncompetitive antagonist with respect to agonists at both α7 nAChRs and N-methyl-D-aspartate receptors. Here, we tested the hypothesis that in hippocampal slices tonically active α7 nAChRs control GABAergic transmission to CA1 pyramidal neurons and are sensitive to inhibition by rising levels of KYNA. The α7 nAChR-selective antagonist α-bungarotoxin (α-BGT; 100 nM) and methyllycaconitine (MLA; 10 nM), an antagonist at α7 and other nAChRs, reduced by 51.3 ± 1.3 and 65.2 ± 1.5%, respectively, the frequency of GABAergic postsynaptic currents (PSCs) recorded from CA1 pyramidal neurons. MLA had no effect on miniature GABAergic PSCs. Thus, GABAergic synaptic activity in CA1 pyramidal neurons is maintained, in part, by tonically active α7 nAChRs located on the preterminal region of axons and/or the somatodendritic region of interneurons that synapse onto the neurons under study. L-Kynurenine (20 or 200 μM) or KYNA (20-200 μM) suppressed concentration-dependently the fre...Continue Reading

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Citations

Nov 20, 2013·Neuroscience and Biobehavioral Reviews·Keith A FeigensonSteven M Silverstein
Dec 29, 2012·Biochemical Pharmacology·Edson X Albuquerque, Robert Schwarcz
Aug 27, 2015·International Journal of Surgery·Aparna Banerjee DixitJyotirmoy Banerjee
Nov 5, 2013·Progress in Neuro-psychopharmacology & Biological Psychiatry·Aye-Mu Myint, Yong-Ku Kim
Jun 6, 2016·Journal of Neural Transmission·Saeed Sadigh-EteghadMahnaz Talebi
May 8, 2014·The Australian and New Zealand Journal of Psychiatry·Justin DavisMichael Berk
Oct 1, 2015·Pharmacological Reviews·Daniel BertrandDiana Donnelly-Roberts
Sep 26, 2020·Frontiers in Cellular Neuroscience·Rebecca StevensonYossi Buskila

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