{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T13:25:56Z","timestamp":1785936356893,"version":"3.56.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,11,8]],"date-time":"2023-11-08T00:00:00Z","timestamp":1699401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT 178043"],"award-info":[{"award-number":["PJT 178043"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["FDN 143210"],"award-info":[{"award-number":["FDN 143210"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The neurodegenerative disorder, Huntington disease (HD), manifests as disorders of movement, cognition and mood. Although studies report abnormal corticostriatal synaptic function early in HD mouse models, less is known about cortical\u2013cortical activity across brain regions and disease stages. Recently, we reported enhanced mesoscale spread of cortical responses to sensory stimulation in vivo at early-manifest stages of two HD mouse models. Here, we investigated cortical excitability of zQ175 HD-model mice compared to their wild-type littermates across different cell types, ages and\/or cortical regions using ex vivo electrophysiology. Cortical pyramidal neurons (CPNs) in somatosensory cortex of zQ175 mice showed intrinsic hyper-excitability at 3\u20134\u00a0months, but hypo-excitability at early-manifest stage (8\u20139\u00a0months); reduced frequency of spontaneous excitatory postsynaptic currents (sEPSCs) was seen at both ages. In contrast, motor cortex CPNs in early-manifest zQ175 mice showed increased intrinsic excitability and sEPSC frequency. Large-amplitude excitatory discharges recorded from CPNs in early-manifest zQ175 mice showed increased frequency only in somatosensory cortex, suggesting the intrinsic hypo-excitability of these CPNs may be compensatory against cortical network hyper-excitability. Similarly, in early-manifest zQ175 mice, region-dependent differences were seen in fast-spiking interneurons (FSIs): somatosensory but not motor FSIs from early-manifest zQ175 mice had reduced intrinsic excitability. Moreover, CPNs showed decreased frequency of spontaneous inhibitory postsynaptic currents and increased excitatory-inhibitory (E-I) balance of evoked synaptic currents in somatosensory cortex. Aberrant large-amplitude discharges and reduced inhibitory drive may therefore underlie E-I imbalances that result in circuit changes and synaptic dysfunction in early-manifest HD.<\/jats:p>","DOI":"10.1093\/hmg\/ddad191","type":"journal-article","created":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T11:17:46Z","timestamp":1699615066000},"page":"387-399","source":"Crossref","is-referenced-by-count":7,"title":["Age- and region-dependent cortical excitability in the zQ175 Huntington disease mouse model"],"prefix":"10.1093","volume":"33","author":[{"given":"Yundi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Djavad Mowafaghian Centre for Brain Health , 2215 Wesbrook Mall, Vancouver, V6T 1Z3 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Ramandi","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Djavad Mowafaghian Centre for Brain Health , 2215 Wesbrook Mall, Vancouver, V6T 1Z3 , Canada"},{"name":"University of British Columbia Graduate Program in Cell and Developmental Biology, , 2350 Health Sciences Mall, Vancouver, V6T 2A1 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marja D","family":"Sepers","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Djavad Mowafaghian Centre for Brain Health , 2215 Wesbrook Mall, Vancouver, V6T 1Z3 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P","family":"Mackay","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Djavad Mowafaghian Centre for Brain Health , 2215 Wesbrook Mall, Vancouver, V6T 1Z3 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn A","family":"Raymond","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Djavad Mowafaghian Centre for Brain Health , 2215 Wesbrook Mall, Vancouver, V6T 1Z3 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,11,8]]},"reference":[{"key":"2024022010050001900_ref1","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-E","article-title":"A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington\u2019s disease chromosomes","volume":"72","author":"MacDonald","year":"1993","journal-title":"Cell"},{"key":"2024022010050001900_ref2","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1177\/1073858420972662","article-title":"Synaptic dysfunction in Huntington\u2019s disease: lessons from genetic animal models","volume":"28","author":"Cepeda","year":"2022","journal-title":"Neuroscientist"},{"key":"2024022010050001900_ref3","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.neuron.2019.05.001","article-title":"Huntingtin lowering strategies for disease modification in Huntington\u2019s 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