{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T04:07:29Z","timestamp":1778126849716,"version":"3.51.4"},"reference-count":100,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T00:00:00Z","timestamp":1648166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Cognitive deficits and impaired sensory processing are hallmarks of several neurodevelopmental and neuropsychiatric disorders. <jats:italic>N<\/jats:italic>\u2010methyl\u2010<jats:sc>d<\/jats:sc>\u2010aspartate receptor (NMDAR) hypofunction contributes to these deficits by disrupting the excitation\u2010to\u2010inhibition balance in neuronal networks. Although preclinical data suggest that the activation of gamma\u2010Aminobutyric acid B receptors (GABA<jats:sub>B<\/jats:sub>R) may restore excitation\u2010to\u2010inhibition balance and rescues some behavioral deficits, GABA<jats:sub>B<\/jats:sub>R agonists have failed to meet their clinical study endpoints, suggesting more complex interactions at play. Here, we studied the effects of Baclofen (a GABA<jats:sub>B<\/jats:sub>R agonist) and MK\u2010801 (a non\u2010competitive NMDAR antagonist) on the neurophysiology of limbic\u2010auditory circuits in freely\u2010moving rats. The pharmacological effects were assessed using resting\u2010state EEG, auditory\u2010evoked oscillation, and mismatch negativity paradigms. MK\u2010801 elevated resting\u2010state oscillatory power, mainly in the gamma and higher frequency ranges, and impaired auditory\u2010evoked responses. Baclofen partially normalized resting\u2010state oscillations but failed to rescue auditory\u2010evoked oscillatory abnormalities. Coherence analysis indicated that NMDAR hypofunction alters the functional coupling of limbic and thalamocortical circuits in several frequency bands. Baclofen normalized only a fraction of MK\u2010801\u2010induced abnormalities (e.g., theta coherence between frontal cortex and amygdala) while reducing delta\u2010theta and augmenting gamma coherence in thalamocortical circuits. Finally, we report that Baclofen intensified the MK\u2010801\u2010induced deficits in auditory mismatch responses. In summary, while Baclofen partially normalizes MK\u2010801\u2010induced gamma abnormalities, it either fails to rescue or exacerbates deficits in other phenotypes like functional coupling and auditory processing. We hope that the presented complex interactions between pharmacologically induced NMDAR hypofunction and GABABR agonism inspire a new understanding of the therapeutic potential around GABAergic modulation.\n<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15602-fig-0007-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.15602","type":"journal-article","created":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T09:19:07Z","timestamp":1646644747000},"page":"417-434","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["<scp>GABA<sub>B<\/sub>R<\/scp> activation partially normalizes acute <scp>NMDAR<\/scp> hypofunction oscillatory abnormalities but fails to rescue sensory processing deficits"],"prefix":"10.1111","volume":"161","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6472-2956","authenticated-orcid":false,"given":"Philipp","family":"Janz","sequence":"first","affiliation":[{"name":"Roche Pharma Research and Early Development, Neuroscience and Rare Diseases, Roche Innovation Center Basel F. 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