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Modulation of circuit oscillations in the rat anterior cingulate cortex (ACC) in vitro by mGlu2 metabotropic glutamate receptors and alleviation of the effects of phencyclidine-induced NMDA-receptor hypofunction

Lookup NU author(s): Bethany Dennis, Dr Stuart Neale, Dr Fiona LeBeauORCiD, Professor Tom Salt

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Abstract

© 2023 The AuthorsAberrant cortical oscillations in the beta and gamma range are associated with symptoms of schizophrenia and other psychiatric conditions. We have thus investigated the ability of anterior cingulate cortex (ACC) in vitro to generate beta and gamma oscillations, and how these are affected by Group II metabotropic glutamate (mGlu) receptor activation and blockade of N-methyl-D-aspartate (NMDA) receptors. Activation of Group II mGlu receptors, and mGlu2 specifically, with orthosteric agonists reduced the power of both beta and gamma oscillations in ACC without a significant effect on oscillation peak frequencies. The NMDA receptor blocker phencyclidine (PCP), known to evoke certain schizophrenia-like symptoms in humans, elevated the power of beta oscillations in ACC and caused a shift in oscillation frequency from the gamma range to the beta range. These enhanced beta oscillations were reduced by the Group II mGlu receptor agonists. These results show that Group II mGlu receptors, and specifically mGlu2, modulate network oscillations. Furthermore, attenuation of the effect of PCP suggests that mGlu2 receptors may stabilise aberrant network activity. These results underline the importance of Group II mGlu receptors, and particularly mGlu2, as targets for the treatment of neuropsychiatric and neurodegenerative diseases.

Publication metadata

Author(s): Dennis BH, Neale SA, LeBeau FEN, Salt TE

Publication type: Article

Publication status: Published

Journal: Pharmacology Biochemistry and Behavior

Year: 2023

Volume: 223

Print publication date: 01/02/2023

Online publication date: 22/02/2023

Acceptance date: 16/02/2023

Date deposited: 21/03/2023

ISSN (print): 0091-3057

ISSN (electronic): 1873-5177

Publisher: Elsevier Inc.

URL: https://doi.org/10.1016/j.pbb.2023.173532

DOI: 10.1016/j.pbb.2023.173532

PubMed id: 36822254

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