Top-down suppression of sensory cortex in an NMDAR hypofunction model of psychosis

Ranson, Adam ORCID: https://orcid.org/0000-0002-4804-0832, Broom, Eluned, Powell, Anna ORCID: https://orcid.org/0000-0003-2070-856X, Chen, Fangli, Major, Guy ORCID: https://orcid.org/0000-0002-4193-6601 and Hall, Jeremy ORCID: https://orcid.org/0000-0003-2737-9009 2019. Top-down suppression of sensory cortex in an NMDAR hypofunction model of psychosis. Schizophrenia Bulletin 45 (6) , pp. 1349-1357. 10.1093/schbul/sby190

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Abstract

Conceptual and computational models have been advanced that propose that perceptual disturbances in psychosis, such as hallucinations, may arise due to a disruption in the balance between bottom-up (ie sensory) and top-down (ie from higher brain areas) information streams in sensory cortex. However, the neural activity underlying this hypothesized alteration remains largely unexplored. Pharmacological N-methyl-D-aspartate receptor (NMDAR) antagonism presents an attractive model to examine potential changes as it acutely recapitulates many of the symptoms of schizophrenia including hallucinations, and NMDAR hypofunction is strongly implicated in the pathogenesis of schizophrenia as evidenced by large-scale genetic studies. Here we use in vivo 2-photon imaging to measure frontal top-down signals from the anterior cingulate cortex (ACC) and their influence on activity of the primary visual cortex (V1) in mice during pharmacologically induced NMDAR hypofunction. We find that global NMDAR hypofunction causes a significant increase in activation of top-down ACC axons, and that surprisingly this is associated with an ACC-dependent net suppression of spontaneous activity in V1 as well as a reduction in V1 sensory-evoked activity. These findings are consistent with a model in which perceptual disturbances in psychosis are caused in part by aberrant top-down frontal cortex activity that suppresses the transmission of sensory signals through early sensory areas.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences Psychology Neuroscience and Mental Health Research Institute (NMHRI) Medicine
Additional Information:	This is an open access article distributed under the terms of the Creative Commons CC BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Publisher:	Oxford University Press
ISSN:	0586-7614
Date of First Compliant Deposit:	30 January 2019
Date of Acceptance:	14 December 2018
Last Modified:	13 May 2023 17:51
URI:	https://orca.cardiff.ac.uk/id/eprint/119036

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