{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:55:21Z","timestamp":1785430521219,"version":"3.56.0"},"posted":{"date-parts":[[2026,5,19]]},"group-title":"Neuroscience","reference-count":54,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"award":["1R01NS110953"],"award-info":[{"award-number":["1R01NS110953"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Motoneurons are under strong pressure to maintain stable motor output throughout an individual life, through homeostatic regulation of their electrical properties. Dysregulated spinal motoneuron excitability has long been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Recent work in SOD1\n                  <jats:sup>G93A<\/jats:sup>\n                  mice suggests that the homeostatic response of motoneurons becomes dysregulated as cellular processes are disrupted by the disease, causing fluctuations in motoneuron electrical properties. Yet, few studies directly test whether ALS motoneurons respond differently than wild type motoneurons to a common chronic perturbation. Here, we used in vivo electrophysiology to test whether motoneurons from pre-symptomatic SOD1\n                  <jats:sup>G93A<\/jats:sup>\n                  mice modulate excitability differently than wild type motoneurons in response to the same homeostatic perturbation: chronic inhibition exerted by the benzodiazepine diazepam. Using linear mixed-effects statistical models, we assessed whether diazepam treatment differentially modulated passive properties, firing behavior, spike properties, and\/or synaptic inputs in SOD1\n                  <jats:sup>G93A<\/jats:sup>\n                  versus wild type motoneurons. We identified a significant genotype \u00d7 treatment interaction effect selectively for properties related to passive membrane integration and spike initiation, including membrane time constant, peak input resistance, and recruitment current. In contrast, firing gain, spike waveform characteristics, and synaptic inputs were largely unaffected. These findings indicate that sustained inhibitory perturbation selectively triggered overactive intrinsic compensatory mechanisms in SOD1\n                  <jats:sup>G93A<\/jats:sup>\n                  motoneurons rather than inducing widespread changes in firing or synaptic transmission. Together, our results provide direct evidence for over-active homeostatic control of motoneuron excitability and support a view of motoneuron dysfunction in ALS as a problem of altered feedback regulation rather than simply hyper- or hypo-excitability.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Abstract Figure<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" fig-type=\"figure\" orientation=\"portrait\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"725609v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.64898\/2026.05.16.725609","type":"posted-content","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T18:05:20Z","timestamp":1779213920000},"source":"Crossref","is-referenced-by-count":0,"title":["Chronic diazepam reveals excessive homeostatic gain in SOD1\n                  <sup>G93A<\/sup>\n                  mouse spinal motoneurons"],"prefix":"10.64898","author":[{"given":"Emily","family":"Reedich","sequence":"first","affiliation":[{"name":"George and Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI"},{"name":"Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Tzai","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Imhoff-Manuel","sequence":"additional","affiliation":[{"name":"George and Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI"},{"name":"Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5344-3572","authenticated-orcid":false,"given":"Marin","family":"Manuel","sequence":"additional","affiliation":[{"name":"George and Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI"},{"name":"Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026052204351140000_2026.05.16.725609v1.1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21543"},{"key":"2026052204351140000_2026.05.16.725609v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2006.05.002"},{"key":"2026052204351140000_2026.05.16.725609v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2003.07.010"},{"key":"2026052204351140000_2026.05.16.725609v1.4","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.074138"},{"key":"2026052204351140000_2026.05.16.725609v1.5","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00665.2003"},{"key":"2026052204351140000_2026.05.16.725609v1.6","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1340-08.2008"},{"key":"2026052204351140000_2026.05.16.725609v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2013.02.011"},{"key":"2026052204351140000_2026.05.16.725609v1.8","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.265843"},{"key":"2026052204351140000_2026.05.16.725609v1.9","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.200659"},{"key":"2026052204351140000_2026.05.16.725609v1.10","doi-asserted-by":"publisher","DOI":"10.1113\/JP275498"},{"key":"2026052204351140000_2026.05.16.725609v1.11","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.30955"},{"key":"2026052204351140000_2026.05.16.725609v1.12","doi-asserted-by":"publisher","DOI":"10.1002\/STEM.2354"},{"key":"2026052204351140000_2026.05.16.725609v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2016.09.014"},{"key":"2026052204351140000_2026.05.16.725609v1.14","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-031-07167-6_4"},{"key":"2026052204351140000_2026.05.16.725609v1.15","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00045.2017"},{"key":"2026052204351140000_2026.05.16.725609v1.16","doi-asserted-by":"publisher","DOI":"10.1113\/jp284192"},{"key":"2026052204351140000_2026.05.16.725609v1.17","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-65685-8"},{"key":"2026052204351140000_2026.05.16.725609v1.18","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0378-20.2021"},{"key":"2026052204351140000_2026.05.16.725609v1.19","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23224-7"},{"key":"2026052204351140000_2026.05.16.725609v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2013.10.003"},{"key":"2026052204351140000_2026.05.16.725609v1.21","doi-asserted-by":"crossref","unstructured":"C. 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