{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:39:17Z","timestamp":1791329957675,"version":"4.3.1"},"reference-count":69,"publisher":"Society for Neuroscience","issue":"43","license":[{"start":{"date-parts":[[2009,4,22]],"date-time":"2009-04-22T00:00:00Z","timestamp":1240358400000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2008,10,22]]},"abstract":"<jats:p>Distinguishing the primary from secondary effects and compensatory mechanisms is of crucial importance in understanding adult-onset neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Transgenic mice that overexpress the G93A mutation of the human Cu-Zn superoxide dismutase 1 gene (hSOD1<jats:sup>G93A<\/jats:sup>mice) are a commonly used animal model of ALS. Whole-cell patch-clamp recordings from neurons in acute slice preparations from neonatal wild-type and hSOD1<jats:sup>G93A<\/jats:sup>mice were made to characterize functional changes in neuronal activity. Hypoglossal motoneurons (HMs) in postnatal day 4 (P4)\u2013P10 hSOD1<jats:sup>G93A<\/jats:sup>mice displayed hyperexcitability, increased persistent Na<jats:sup>+<\/jats:sup>current (PC<jats:sub>Na<\/jats:sub>), and enhanced frequency of spontaneous excitatory and inhibitory transmission, compared with wild-type mice. These functional changes in neuronal activity are the earliest yet reported for the hSOD1<jats:sup>G93A<\/jats:sup>mouse, and are present 2\u20133 months before motoneuron degeneration and clinical symptoms appear in these mice. Changes in neuronal activity were not restricted to motoneurons: superior colliculus interneurons also displayed hyperexcitability and synaptic changes (P10\u2013P12). Furthermore,<jats:italic>in vivo<\/jats:italic>viral-mediated GFP (green fluorescent protein) overexpression in hSOD1<jats:sup>G93A<\/jats:sup>HMs revealed precocious dendritic remodeling, and behavioral assays revealed transient neonatal neuromotor deficits compared with controls. These findings underscore the widespread and early onset of abnormal neural activity in this mouse model of the adult neurodegenerative disease ALS, and suggest that suppression of PC<jats:sub>Na<\/jats:sub>and hyperexcitability early in life might be one way to mitigate or prevent cell death in the adult CNS.<\/jats:p>","DOI":"10.1523\/jneurosci.1340-08.2008","type":"journal-article","created":{"date-parts":[[2008,10,22]],"date-time":"2008-10-22T17:39:55Z","timestamp":1224697195000},"page":"10864-10874","source":"Crossref","is-referenced-by-count":233,"title":["Neonatal Neuronal Circuitry Shows Hyperexcitable Disturbance in a Mouse Model of the Adult-Onset Neurodegenerative Disease Amyotrophic Lateral Sclerosis"],"prefix":"10.1523","volume":"28","author":[{"given":"Brigitte","family":"van Zundert","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieke H.","family":"Peuscher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meri","family":"Hynynen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael L.","family":"Neve","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Robert H.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha","family":"Constantine-Paton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark C.","family":"Bellingham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2008,10,22]]},"reference":[{"key":"2023041303344223000_28.43.10864.1","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1152\/jn.2000.83.3.1580","article-title":"Chronic NMDA exposure accelerates development of GABAergic inhibition in the superior colliculus","volume":"83","author":"Aamodt","year":"2000","journal-title":"J Neurophysiol"},{"key":"2023041303344223000_28.43.10864.2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2001.013371"},{"key":"2023041303344223000_28.43.10864.3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2004.03745.x"},{"key":"2023041303344223000_28.43.10864.4","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1152\/jn.1998.80.3.1547","article-title":"Activation of protein kinase C increases neuronal excitability by regulating persistent Na+ current in mouse neocortical slices","volume":"80","author":"Astman","year":"1998","journal-title":"J Neurophysiol"},{"key":"2023041303344223000_28.43.10864.5","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1786-04.2005"},{"key":"2023041303344223000_28.43.10864.6","doi-asserted-by":"crossref","first-page":"3758","DOI":"10.1152\/jn.1996.76.6.3758","article-title":"Presynaptic depression of excitatory synaptic inputs to rat hypoglossal motoneurons by muscarinic M2 receptors","volume":"76","author":"Bellingham","year":"1996","journal-title":"J Neurophysiol"},{"key":"2023041303344223000_28.43.10864.7","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(01)00627-X"},{"key":"2023041303344223000_28.43.10864.8","doi-asserted-by":"publisher","DOI":"10.1126\/science.1123511"},{"key":"2023041303344223000_28.43.10864.9","doi-asserted-by":"publisher","DOI":"10.1055\/s-2001-15260"},{"key":"2023041303344223000_28.43.10864.10","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/35077553","article-title":"Neuromodulation of Na+ channels: an unexpected form of cellular plasticity","volume":"2","author":"Cantrell","year":"2001","journal-title":"Nat Rev Neurosci"},{"key":"2023041303344223000_28.43.10864.11","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2000.00050.x"},{"key":"2023041303344223000_28.43.10864.12","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.20.2269"},{"key":"2023041303344223000_28.43.10864.13","doi-asserted-by":"publisher","DOI":"10.1126\/science.1086071"},{"key":"2023041303344223000_28.43.10864.14","doi-asserted-by":"publisher","DOI":"10.1038\/35097565"},{"key":"2023041303344223000_28.43.10864.15","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00049.2002"},{"key":"2023041303344223000_28.43.10864.16","doi-asserted-by":"publisher","DOI":"10.1126\/science.1090349"},{"key":"2023041303344223000_28.43.10864.17","doi-asserted-by":"publisher","DOI":"10.1038\/nn1885"},{"key":"2023041303344223000_28.43.10864.18","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903570305"},{"key":"2023041303344223000_28.43.10864.19","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020221919154"},{"key":"2023041303344223000_28.43.10864.20","doi-asserted-by":"publisher","DOI":"10.1038\/377232a0"},{"key":"2023041303344223000_28.43.10864.21","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1999.tb11272.x"},{"key":"2023041303344223000_28.43.10864.22","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.059972"},{"key":"2023041303344223000_28.43.10864.23","doi-asserted-by":"publisher","DOI":"10.1126\/science.8209258"},{"key":"2023041303344223000_28.43.10864.24","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3278-04.2004"},{"key":"2023041303344223000_28.43.10864.25","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.01845.x"},{"key":"2023041303344223000_28.43.10864.26","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.01670.x"},{"key":"2023041303344223000_28.43.10864.27","doi-asserted-by":"crossref","first-page":"8042","DOI":"10.1523\/JNEUROSCI.22-18-08042.2002","article-title":"The AMPA receptor subunit GluR1 regulates dendritic architecture of motor neurons","volume":"22","author":"Inglis","year":"2002","journal-title":"J Neurosci"},{"key":"2023041303344223000_28.43.10864.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2004.06.014"},{"key":"2023041303344223000_28.43.10864.29","doi-asserted-by":"crossref","first-page":"3063","DOI":"10.1242\/dev.120.11.3063","article-title":"Regulation of motor neuron dendrite growth by NMDA receptor activation","volume":"120","author":"Kalb","year":"1994","journal-title":"Development"},{"key":"2023041303344223000_28.43.10864.30","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1111\/j.1749-6632.2002.tb02807.x","article-title":"Differential susceptibility of the ocular motor system to disease","volume":"956","author":"Kaminski","year":"2002","journal-title":"Ann N Y Acad Sci"},{"key":"2023041303344223000_28.43.10864.31","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M002043200"},{"key":"2023041303344223000_28.43.10864.32","doi-asserted-by":"publisher","DOI":"10.1038\/nn2040"},{"key":"2023041303344223000_28.43.10864.33","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00665.2003"},{"key":"2023041303344223000_28.43.10864.34","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.074138"},{"key":"2023041303344223000_28.43.10864.35","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19980629)396:2<158::AID-CNE2>3.0.CO;2-#"},{"key":"2023041303344223000_28.43.10864.36","doi-asserted-by":"publisher","DOI":"10.1126\/science.288.5464.335"},{"key":"2023041303344223000_28.43.10864.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.06.031"},{"key":"2023041303344223000_28.43.10864.38","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh132"},{"key":"2023041303344223000_28.43.10864.39","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/121.5.851"},{"key":"2023041303344223000_28.43.10864.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2003.11.004"},{"key":"2023041303344223000_28.43.10864.41","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19980202)391:1<64::AID-CNE6>3.0.CO;2-P"},{"key":"2023041303344223000_28.43.10864.42","first-page":"15","article-title":"Clinical limits of amyotrophic lateral sclerosis","volume":"36","author":"Mulder","year":"1982","journal-title":"Adv Neurol"},{"key":"2023041303344223000_28.43.10864.43","doi-asserted-by":"publisher","DOI":"10.1038\/nn1876"},{"key":"2023041303344223000_28.43.10864.44","doi-asserted-by":"crossref","first-page":"381","DOI":"10.2144\/05393PS01","article-title":"Use of herpes virus amplicon vectors to study brain disorders","volume":"39","author":"Neve","year":"2005","journal-title":"BioTechniques"},{"key":"2023041303344223000_28.43.10864.45","doi-asserted-by":"publisher","DOI":"10.1126\/science.1656525"},{"key":"2023041303344223000_28.43.10864.46","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903390308"},{"key":"2023041303344223000_28.43.10864.47","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1152\/jn.1999.82.3.1638","article-title":"Cotransmission of GABA and glycine to brain stem motoneurons","volume":"82","author":"O'Brien","year":"1999","journal-title":"J Neurophysiol"},{"key":"2023041303344223000_28.43.10864.48","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0345-05.2005"},{"key":"2023041303344223000_28.43.10864.49","doi-asserted-by":"publisher","DOI":"10.1038\/nature05289"},{"key":"2023041303344223000_28.43.10864.50","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1971"},{"key":"2023041303344223000_28.43.10864.51","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1996.0107"},{"key":"2023041303344223000_28.43.10864.52","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00241.2002"},{"key":"2023041303344223000_28.43.10864.53","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1523\/JNEUROSCI.19-05-01663.1999","article-title":"Ionic currents underlying spontaneous action potentials in isolated cerebellar Purkinje neurons","volume":"19","author":"Raman","year":"1999","journal-title":"J Neurosci"},{"key":"2023041303344223000_28.43.10864.54","doi-asserted-by":"publisher","DOI":"10.1038\/362059a0"},{"key":"2023041303344223000_28.43.10864.55","doi-asserted-by":"crossref","first-page":"6264","DOI":"10.1523\/JNEUROSCI.17-16-06264.1997","article-title":"Temporal correlations between functional and molecular changes in NMDA receptors and GABA neurotransmission in the superior colliculus","volume":"17","author":"Shi","year":"1997","journal-title":"J Neurosci"},{"key":"2023041303344223000_28.43.10864.56","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)00089-1"},{"key":"2023041303344223000_28.43.10864.57","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2007.10.017"},{"key":"2023041303344223000_28.43.10864.58","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2005.12.003"},{"key":"2023041303344223000_28.43.10864.59","doi-asserted-by":"publisher","DOI":"10.1016\/j.devbrainres.2003.11.002"},{"key":"2023041303344223000_28.43.10864.60","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0335786100"},{"key":"2023041303344223000_28.43.10864.61","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1207-04.2004"},{"key":"2023041303344223000_28.43.10864.62","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1327"},{"key":"2023041303344223000_28.43.10864.63","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2000.00242.x"},{"key":"2023041303344223000_28.43.10864.64","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2004.05.010"},{"key":"2023041303344223000_28.43.10864.65","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2005.07.001"},{"key":"2023041303344223000_28.43.10864.66","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl172"},{"key":"2023041303344223000_28.43.10864.67","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn071"},{"key":"2023041303344223000_28.43.10864.68","doi-asserted-by":"publisher","DOI":"10.2174\/1389450013348489"},{"key":"2023041303344223000_28.43.10864.69","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2007.05456.x"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.1340-08.2008","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T18:55:27Z","timestamp":1681412127000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.1340-08.2008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,10,22]]},"references-count":69,"journal-issue":{"issue":"43","published-online":{"date-parts":[[2008,10,22]]},"published-print":{"date-parts":[[2008,10,22]]}},"alternative-id":["10.1523\/JNEUROSCI.1340-08.2008"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.1340-08.2008","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,10,22]]}}}