{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:34:57Z","timestamp":1790696097904,"version":"4.1.0"},"reference-count":59,"publisher":"Society for Neuroscience","issue":"18","license":[{"start":{"date-parts":[[2006,11,3]],"date-time":"2006-11-03T00:00:00Z","timestamp":1162512000000},"content-version":"vor","delay-in-days":184,"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":[[2006,5,3]]},"abstract":"<jats:p><jats:italic>Spastic<\/jats:italic>(<jats:italic>spa<\/jats:italic>),<jats:italic>spasmodic<\/jats:italic>(<jats:italic>spd<\/jats:italic>), and<jats:italic>oscillator<\/jats:italic>(<jats:italic>ot<\/jats:italic>) mice have naturally occurring glycine receptor (GlyR) mutations, which manifest as motor deficits and an exaggerated \u201cstartle response.\u201d Using whole-cell recording in hypoglossal motoneurons, we compared the physiological mechanisms by which each mutation alters GlyR function. Mean glycinergic miniature IPSC (mIPSC) amplitude and frequency were dramatically reduced (&gt;50%) compared with controls for each mutant. mIPSC decay times were unchanged in<jats:italic>spa\/spa<\/jats:italic>(4.5 \u00b1 0.3 vs 4.7 \u00b1 0.2 ms), reduced in<jats:italic>spd\/spd<\/jats:italic>(2.7 \u00b1 0.2 vs 4.7 \u00b1 0.2 ms), and increased in<jats:italic>ot\/ot<\/jats:italic>(12.3 \u00b1 1.2 vs 4.8 \u00b1 0.2 ms). Thus, in<jats:italic>spastic<\/jats:italic>, GlyRs are functionally normal but reduced in number, whereas in<jats:italic>spasmodic<\/jats:italic>, GlyR kinetics is faster. The<jats:italic>oscillator<\/jats:italic>mutation results in complete absence of \u03b11-containing GlyRs; however, some non-\u03b11-containing GlyRs persist at synapses. Fluctuation analysis of membrane current, induced by glycine application to outside-out patches, showed that mean single-channel conductance was increased in<jats:italic>spa\/spa<\/jats:italic>(64.2 \u00b1 4.9 vs 36.1 \u00b1 1.4 pS), but unchanged in<jats:italic>spd\/spd<\/jats:italic>(32.4 \u00b1 2.1 vs 35.3 \u00b1 2.1 pS). GlyR-mediated whole-cell currents in<jats:italic>spa\/spa<\/jats:italic>exhibited increased picrotoxin sensitivity (27 vs 71% block for 100 \u03bc<jats:sc>m<\/jats:sc>), indicating \u03b11 homomeric GlyR expression. The picrotoxin sensitivity of evoked glycinergic IPSCs and conductance of synaptic GlyRs, as determined by nonstationary variance analysis, were identical for<jats:italic>spa\/spa<\/jats:italic>and controls. Together, these findings show the three mutations disrupt GlyR-mediated inhibition via different physiological mechanisms, and the<jats:italic>spastic<\/jats:italic>mutation results in \u201ccompensatory\u201d \u03b11 homomeric GlyRs at extrasynaptic loci.<\/jats:p>","DOI":"10.1523\/jneurosci.3991-05.2006","type":"journal-article","created":{"date-parts":[[2006,5,3]],"date-time":"2006-05-03T20:24:13Z","timestamp":1146687853000},"page":"4880-4890","source":"Crossref","is-referenced-by-count":53,"title":["Distinct Physiological Mechanisms Underlie Altered Glycinergic Synaptic Transmission in the Murine Mutants<i>spastic<\/i>,<i>spasmodic<\/i>, and<i>oscillator<\/i>"],"prefix":"10.1523","volume":"26","author":[{"given":"Brett A.","family":"Graham","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Schofield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj","family":"Sah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Troy W.","family":"Margrie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Callister","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2006,5,3]]},"reference":[{"key":"2023041303180953000_26.18.4880.1","doi-asserted-by":"crossref","first-page":"2767","DOI":"10.1096\/fasebj.4.10.2165011","volume":"4","year":"(1990)","journal-title":"FASEB J"},{"key":"2023041303180953000_26.18.4880.2","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1523\/JNEUROSCI.06-05-01358.1986","volume":"6","year":"(1986)","journal-title":"J Neurosci"},{"key":"2023041303180953000_26.18.4880.3","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(92)90295-O"},{"key":"2023041303180953000_26.18.4880.4","doi-asserted-by":"publisher","DOI":"10.1038\/341230a0"},{"key":"2023041303180953000_26.18.4880.5","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1113\/jphysiol.1986.sp016253","volume":"379","year":"(1986)","journal-title":"J Physiol (Lond)"},{"key":"2023041303180953000_26.18.4880.6","doi-asserted-by":"crossref","first-page":"3729","DOI":"10.1002\/j.1460-2075.1993.tb06050.x","volume":"12","year":"(1993)","journal-title":"EMBO J"},{"key":"2023041303180953000_26.18.4880.7","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/3.11.2025"},{"key":"2023041303180953000_26.18.4880.8","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1681.1999.03148.x"},{"key":"2023041303180953000_26.18.4880.9","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1093\/oxfordjournals.jhered.a107083","volume":"52","year":"(1961)","journal-title":"J Hered"},{"key":"2023041303180953000_26.18.4880.10","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(97)78062-7"},{"key":"2023041303180953000_26.18.4880.11","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1556"},{"key":"2023041303180953000_26.18.4880.12","doi-asserted-by":"crossref","first-page":"9698","DOI":"10.1523\/JNEUROSCI.19-22-09698.1999","volume":"19","year":"(1999)","journal-title":"J Neurosci"},{"key":"2023041303180953000_26.18.4880.13","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.1152\/jn.2000.84.6.2715","volume":"84","year":"(2000)","journal-title":"J Neurophysiol"},{"key":"2023041303180953000_26.18.4880.14","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1625"},{"key":"2023041303180953000_26.18.4880.15","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5392.1321"},{"key":"2023041303180953000_26.18.4880.16","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80433-X"},{"key":"2023041303180953000_26.18.4880.17","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.049064"},{"key":"2023041303180953000_26.18.4880.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.01.028"},{"key":"2023041303180953000_26.18.4880.19","doi-asserted-by":"publisher","DOI":"10.1007\/BF00656997"},{"key":"2023041303180953000_26.18.4880.20","doi-asserted-by":"publisher","DOI":"10.1016\/0169-328X(95)00218-H"},{"key":"2023041303180953000_26.18.4880.21","doi-asserted-by":"publisher","DOI":"10.1126\/science.1094925"},{"key":"2023041303180953000_26.18.4880.22","unstructured":"Hille B (1992) In: Ionic channels of excitable membranes Sunderland, MA: Sinauer."},{"key":"2023041303180953000_26.18.4880.23","unstructured":"Katz B (1969) In: The release of neural transmitter substances Liverpool, UK: Liverpool UP."},{"key":"2023041303180953000_26.18.4880.24","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1523\/JNEUROSCI.22-04-01328.2002","volume":"22","year":"(2002)","journal-title":"J Neurosci"},{"key":"2023041303180953000_26.18.4880.25","doi-asserted-by":"publisher","DOI":"10.1038\/ng0694-136"},{"key":"2023041303180953000_26.18.4880.26","doi-asserted-by":"crossref","first-page":"4148","DOI":"10.1523\/JNEUROSCI.15-06-04148.1995","volume":"15","year":"(1995)","journal-title":"J Neurosci"},{"key":"2023041303180953000_26.18.4880.27","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(96)00567-2"},{"key":"2023041303180953000_26.18.4880.28","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1093\/oxfordjournals.jhered.a110414","volume":"78","year":"(1987)","journal-title":"J Hered"},{"key":"2023041303180953000_26.18.4880.29","doi-asserted-by":"publisher","DOI":"10.1007\/PL00000899"},{"key":"2023041303180953000_26.18.4880.30","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00042.2003"},{"key":"2023041303180953000_26.18.4880.31","doi-asserted-by":"crossref","first-page":"2401","DOI":"10.1002\/j.1460-2075.1991.tb07779.x","volume":"10","year":"(1991)","journal-title":"EMBO J"},{"key":"2023041303180953000_26.18.4880.32","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90145-0"},{"key":"2023041303180953000_26.18.4880.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2005.05.030"},{"key":"2023041303180953000_26.18.4880.34","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2001.013147"},{"key":"2023041303180953000_26.18.4880.35","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(94)90265-8"},{"key":"2023041303180953000_26.18.4880.36","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.2000.0934"},{"key":"2023041303180953000_26.18.4880.37","doi-asserted-by":"crossref","first-page":"4305","DOI":"10.1002\/j.1460-2075.1992.tb05529.x","volume":"11","year":"(1992)","journal-title":"EMBO J"},{"key":"2023041303180953000_26.18.4880.38","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(95)93880-7"},{"key":"2023041303180953000_26.18.4880.39","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7258(96)00163-5"},{"key":"2023041303180953000_26.18.4880.40","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90251-1"},{"key":"2023041303180953000_26.18.4880.41","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.7.853"},{"key":"2023041303180953000_26.18.4880.42","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/S0006-3495(91)82223-8","volume":"59","year":"(1991)","journal-title":"Biophys J"},{"key":"2023041303180953000_26.18.4880.43","doi-asserted-by":"publisher","DOI":"10.1038\/ng0694-131"},{"key":"2023041303180953000_26.18.4880.44","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(94)00736-5"},{"key":"2023041303180953000_26.18.4880.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2004.03.005"},{"key":"2023041303180953000_26.18.4880.46","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1113\/jphysiol.1980.sp013426","volume":"307","year":"(1980)","journal-title":"J Physiol (Lond)"},{"key":"2023041303180953000_26.18.4880.47","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1212\/WNL.45.10.1883","volume":"45","year":"(1995)","journal-title":"Neurology"},{"key":"2023041303180953000_26.18.4880.48","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1152\/jn.1999.81.4.1608","volume":"81","year":"(1999)","journal-title":"J Neurophysiol"},{"key":"2023041303180953000_26.18.4880.49","doi-asserted-by":"crossref","first-page":"2608","DOI":"10.1152\/jn.1998.80.5.2608","volume":"80","year":"(1998)","journal-title":"J Neurophysiol"},{"key":"2023041303180953000_26.18.4880.50","unstructured":"Sokal R, Rohlf F (1995) In: Biometry: the principles and practice of statistics in biological research Ed 3 New York: Freeman."},{"key":"2023041303180953000_26.18.4880.51","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(92)90073-M"},{"key":"2023041303180953000_26.18.4880.52","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(93)90184-S"},{"key":"2023041303180953000_26.18.4880.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2005.01.001"},{"key":"2023041303180953000_26.18.4880.54","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(98)01341-1"},{"key":"2023041303180953000_26.18.4880.55","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1152\/jn.1993.69.5.1769","volume":"69","year":"(1993)","journal-title":"J Neurophysiol"},{"key":"2023041303180953000_26.18.4880.56","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1152\/jn.1995.73.3.1192","volume":"73","year":"(1995)","journal-title":"J Neurophysiol"},{"key":"2023041303180953000_26.18.4880.57","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(94)90105-8"},{"key":"2023041303180953000_26.18.4880.58","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(03)00499-3"},{"key":"2023041303180953000_26.18.4880.59","doi-asserted-by":"publisher","DOI":"10.1038\/298655a0"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.3991-05.2006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T17:25:23Z","timestamp":1681406723000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.3991-05.2006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,5,3]]},"references-count":59,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2006,5,3]]},"published-print":{"date-parts":[[2006,5,3]]}},"alternative-id":["10.1523\/JNEUROSCI.3991-05.2006"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.3991-05.2006","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,5,3]]}}}