{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T02:34:09Z","timestamp":1793327649037,"version":"4.5.0"},"reference-count":77,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T00:00:00Z","timestamp":1740096000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Project ALS"},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["SI-1969\/2-1"],"award-info":[{"award-number":["SI-1969\/2-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["SI-1969\/3-1"],"award-info":[{"award-number":["SI-1969\/3-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019721","name":"ROCHE","doi-asserted-by":"publisher","award":["R01-NS102451"],"award-info":[{"award-number":["R01-NS102451"]}],"id":[{"id":"10.13039\/100019721","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019721","name":"ROCHE","doi-asserted-by":"publisher","award":["R01-NS114218"],"award-info":[{"award-number":["R01-NS114218"]}],"id":[{"id":"10.13039\/100019721","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019721","name":"ROCHE","doi-asserted-by":"publisher","award":["R01-NS116400"],"award-info":[{"award-number":["R01-NS116400"]}],"id":[{"id":"10.13039\/100019721","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000894","name":"SMA Foundation","doi-asserted-by":"publisher","award":["R35 NS122306"],"award-info":[{"award-number":["R35 NS122306"]}],"id":[{"id":"10.13039\/100000894","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000894","name":"SMA Foundation","doi-asserted-by":"publisher","award":["K12HD001399"],"award-info":[{"award-number":["K12HD001399"]}],"id":[{"id":"10.13039\/100000894","id-type":"DOI","asserted-by":"publisher"}]},{"name":"American SIDS Institute"},{"DOI":"10.13039\/100028898","name":"Raynor Cerebellum Project","doi-asserted-by":"publisher","award":["K01-HD084690"],"award-info":[{"award-number":["K01-HD084690"]}],"id":[{"id":"10.13039\/100028898","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007721","name":"Cure SMA","doi-asserted-by":"publisher","award":["CU18-2886"],"award-info":[{"award-number":["CU18-2886"]}],"id":[{"id":"10.13039\/100007721","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Grant from F. Hoffmann\u2013La Roche"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by a varying degree of severity that is correlated with the reduction of SMN protein levels. Motor neuron degeneration and skeletal muscle atrophy are hallmarks of SMA, but it is unknown whether other mechanisms contribute to the spectrum of clinical phenotypes.<\/jats:p>\n                  <jats:p>Here, through a combination of physiological and morphological studies in mouse models and SMA patients, we identify dysfunction and loss of proprioceptive sensory synapses as key signatures of SMA pathology. We demonstrate that type 3 SMA patients exhibit impaired proprioception and that their proprioceptive synapses are dysfunctional as measured by the neurophysiological test of the Hoffmann reflex. We also show moderate loss of spinal motor neurons along with reduced excitatory afferent synapses and altered potassium channel expression in motor neurons from type 1 SMA patients. These are conserved pathogenic events found in both severely affected patients and mouse models. Lastly, we report that improved motor function and fatigability in ambulatory type 3 SMA patients and mouse models treated with SMN-inducing drugs are correlated with increased function of sensory\u2013motor circuits that can be captured accurately by the Hoffmann reflex assay.<\/jats:p>\n                  <jats:p>Thus, sensory synaptic dysfunction is a clinically relevant event in SMA, and the Hoffmann reflex is a suitable assay to monitor disease progression and treatment efficacy of motor circuit pathology.<\/jats:p>","DOI":"10.1093\/brain\/awaf074","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T23:19:05Z","timestamp":1740007145000},"page":"2797-2811","source":"Crossref","is-referenced-by-count":14,"title":["Proprioceptive synaptic dysfunction is a key feature in mice and humans with spinal muscular atrophy"],"prefix":"10.1093","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3996-4697","authenticated-orcid":false,"given":"Christian M","family":"Simon","sequence":"first","affiliation":[{"name":"Center for Motor Neuron Biology and Disease, Columbia University , New York, NY 10032 ,","place":["USA"]},{"name":"Department of Neurology, Columbia University , New York, NY 10032 ,","place":["USA"]},{"name":"Carl-Ludwig-Institute for Physiology, Leipzig University , Leipzig, Saxony 04103 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Delestr\u00e9e","sequence":"additional","affiliation":[{"name":"Center for Motor Neuron Biology and Disease, Columbia University , New York, NY 10032 ,","place":["USA"]},{"name":"Department of Neurology, Columbia University , New York, NY 10032 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7357-0819","authenticated-orcid":false,"given":"Jacqueline","family":"Montes","sequence":"additional","affiliation":[{"name":"Center for Motor Neuron Biology and Disease, Columbia University , New York, NY 10032 ,","place":["USA"]},{"name":"Department of Rehabilitation and Regenerative Medicine, Columbia University , New York, NY 10032 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonie","family":"Sowoidnich","sequence":"additional","affiliation":[{"name":"Center for Motor Neuron Biology and Disease, Columbia University , New York, NY 10032 ,","place":["USA"]},{"name":"Department of Neurology, Columbia University , New York, NY 10032 ,","place":["USA"]},{"name":"Carl-Ludwig-Institute for Physiology, Leipzig University , Leipzig, Saxony 04103 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Gerstner","sequence":"additional","affiliation":[{"name":"Carl-Ludwig-Institute for Physiology, Leipzig University , Leipzig, Saxony 04103 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erick","family":"Carranza","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Pittsburgh , Pittsburgh, PA 15213 ,","place":["USA"]},{"name":"Rehab Neural Engineering Labs, University of Pittsburgh , Pittsburgh, PA 15219 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jannik M","family":"Buettner","sequence":"additional","affiliation":[{"name":"Carl-Ludwig-Institute for Physiology, Leipzig University , Leipzig, Saxony 04103 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G","family":"Pagiazitis","sequence":"additional","affiliation":[{"name":"Center for Motor Neuron Biology and Disease, Columbia University , New York, NY 10032 ,","place":["USA"]},{"name":"Department of Neurology, Columbia University , New York, NY 10032 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genis","family":"Prat-Ortega","sequence":"additional","affiliation":[{"name":"Rehab Neural Engineering Labs, University of Pittsburgh , Pittsburgh, PA 15219 ,","place":["USA"]},{"name":"Department of Neurological Surgery, University of Pittsburgh , Pittsburgh, PA 15213 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Ensel","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Pittsburgh , Pittsburgh, PA 15213 ,","place":["USA"]},{"name":"Rehab Neural Engineering Labs, University of Pittsburgh , Pittsburgh, PA 15219 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Donadio","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Pittsburgh , Pittsburgh, PA 15213 ,","place":["USA"]},{"name":"Rehab Neural Engineering Labs, University of Pittsburgh , Pittsburgh, PA 15219 ,","place":["USA"]},{"name":"Department of Neurological Surgery, University of Pittsburgh , Pittsburgh, PA 15213 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Dreilich","sequence":"additional","affiliation":[{"name":"Carl-Ludwig-Institute for Physiology, Leipzig University , Leipzig, Saxony 04103 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J","family":"Carlini","sequence":"additional","affiliation":[{"name":"Center for Motor Neuron Biology and Disease, Columbia University , New York, NY 10032 ,","place":["USA"]},{"name":"Department of Neurology, Columbia University , New York, NY 10032 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose L","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Neurology, Columbia University , New York, NY 10032 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiotis","family":"Kratimenos","sequence":"additional","affiliation":[{"name":"Center for Neuroscience Research, Children\u2019s National Research Institute , Washington, DC 20012 ,","place":["USA"]},{"name":"Department of Pediatrics, George Washington University School of Medicine , Washington, DC 20012 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy K","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Boston Children\u2019s Hospital and Harvard Medical School , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte J","family":"Sumner","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins University School of Medicine , Baltimore, MD 21205 ,","place":["USA"]},{"name":"Department of Neuroscience, Johns Hopkins University School of Medicine , Baltimore, MD 21205 ,","place":["USA"]},{"name":"Department of Genetic Medicine, Johns Hopkins University School of Medicine , Baltimore, MD 21218 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis H","family":"Weimer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Columbia University , New York, NY 10032 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8078-3951","authenticated-orcid":false,"given":"Elvira","family":"Pirondini","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Pittsburgh , Pittsburgh, PA 15213 ,","place":["USA"]},{"name":"Rehab Neural Engineering Labs, University of Pittsburgh , Pittsburgh, PA 15219 ,","place":["USA"]},{"name":"University of Pittsburgh Clinical and Translational Science Institute (CTSI) , Pittsburgh, PA 15213 ,","place":["USA"]},{"name":"Department of Physical Medicine and Rehabilitation, University of Pittsburgh , Pittsburgh, PA 15213 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Capogrosso","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Pittsburgh , Pittsburgh, PA 15213 ,","place":["USA"]},{"name":"Rehab Neural Engineering Labs, University of Pittsburgh , Pittsburgh, PA 15219 ,","place":["USA"]},{"name":"Department of Neurological Surgery, University of Pittsburgh , Pittsburgh, PA 15213 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livio","family":"Pellizzoni","sequence":"additional","affiliation":[{"name":"Center for Motor Neuron Biology and Disease, Columbia University , New York, NY 10032 ,","place":["USA"]},{"name":"Department of Neurology, Columbia University , New York, NY 10032 ,","place":["USA"]},{"name":"Department of Pathology and Cell Biology, Columbia University , New York, NY 10032 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darryl C","family":"De Vivo","sequence":"additional","affiliation":[{"name":"Center for Motor Neuron Biology and Disease, Columbia University , New York, NY 10032 ,","place":["USA"]},{"name":"Department of Neurology, Columbia University , New York, NY 10032 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4610-2016","authenticated-orcid":false,"given":"George Z","family":"Mentis","sequence":"additional","affiliation":[{"name":"Center for Motor Neuron Biology and Disease, Columbia University , New York, NY 10032 ,","place":["USA"]},{"name":"Department of Neurology, Columbia University , New York, NY 10032 ,","place":["USA"]},{"name":"Department of Pathology and Cell Biology, Columbia University , New York, NY 10032 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,2,21]]},"reference":[{"key":"2025080112511347700_awaf074-B1","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.neuron.2010.12.032","article-title":"Early functional impairment of sensory-motor connectivity in a mouse model of spinal muscular atrophy","volume":"69","author":"Mentis","year":"2011","journal-title":"Neuron"},{"key":"2025080112511347700_awaf074-B2","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1038\/nn.4561","article-title":"Reduced sensory synaptic excitation impairs motor neuron function via Kv2.1 in spinal muscular atrophy","volume":"20","author":"Fletcher","year":"2017","journal-title":"Nat Neurosci"},{"key":"2025080112511347700_awaf074-B3","doi-asserted-by":"crossref","first-page":"59","DOI":"10.3389\/fnmol.2019.00059","article-title":"Molecular mechanisms underlying sensory-motor circuit dysfunction in SMA","volume":"12","author":"Shorrock","year":"2019","journal-title":"Front Mol Neurosci"},{"key":"2025080112511347700_awaf074-B4","doi-asserted-by":"crossref","first-page":"103376","DOI":"10.1016\/j.isci.2021.103376","article-title":"Central synaptopathy is the most conserved feature of motor circuit pathology across spinal muscular atrophy mouse models","volume":"24","author":"Buettner","year":"2021","journal-title":"iScience"},{"key":"2025080112511347700_awaf074-B5","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/s41572-022-00380-8","article-title":"Spinal muscular atrophy","volume":"8","author":"Mercuri","year":"2022","journal-title":"Nat Rev Dis Primers"},{"key":"2025080112511347700_awaf074-B6","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0092-8674(95)90460-3","article-title":"Identification and characterization of a spinal muscular atrophy-determining gene","volume":"80","author":"Lefebvre","year":"1995","journal-title":"Cell"},{"key":"2025080112511347700_awaf074-B7","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/S1474-4422(12)70061-3","article-title":"Childhood spinal muscular atrophy: Controversies and challenges","volume":"11","author":"Mercuri","year":"2012","journal-title":"Lancet Neurol"},{"key":"2025080112511347700_awaf074-B8","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.nmd.2017.05.011","article-title":"Spinal muscular atrophy: A changing phenotype beyond the clinical trials","volume":"27","author":"Tizzano","year":"2017","journal-title":"Neuromuscul Disord"},{"key":"2025080112511347700_awaf074-B9","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.nmd.2017.11.005","article-title":"Diagnosis and management of spinal muscular atrophy: Part 1: Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care","volume":"28","author":"Mercuri","year":"2018","journal-title":"Neuromuscul Disord"},{"key":"2025080112511347700_awaf074-B10","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/j.nmd.2017.07.007","article-title":"6MWT can identify type 3 SMA patients with neuromuscular junction dysfunction","volume":"27","author":"Pera","year":"2017","journal-title":"Neuromuscul Disord"},{"key":"2025080112511347700_awaf074-B11","doi-asserted-by":"crossref","first-page":"8691","DOI":"10.1523\/JNEUROSCI.0417-15.2015","article-title":"Disease mechanisms and therapeutic approaches in spinal muscular atrophy","volume":"35","author":"Tisdale","year":"2015","journal-title":"J Neurosci"},{"key":"2025080112511347700_awaf074-B12","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1172\/JCI121658","article-title":"Two breakthrough gene-targeted treatments for spinal muscular atrophy: Challenges remain","volume":"128","author":"Sumner","year":"2018","journal-title":"J Clin Invest"},{"key":"2025080112511347700_awaf074-B13","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1056\/NEJMoa1710504","article-title":"Nusinersen versus sham control in later-onset spinal muscular atrophy","volume":"378","author":"Mercuri","year":"2018","journal-title":"N Engl J Med"},{"key":"2025080112511347700_awaf074-B14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejpn.2022.04.006","article-title":"Mid- and long-term (at least 12 months) follow-up of patients with spinal muscular atrophy (SMA) treated with nusinersen, onasemnogene abeparvovec, risdiplam or combination therapies: A systematic review of real-world study data","volume":"39","author":"Erdos","year":"2022","journal-title":"Eur J Paediatr Neurol"},{"key":"2025080112511347700_awaf074-B15","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1056\/NEJMoa1706198","article-title":"Single-dose gene-replacement therapy for spinal muscular atrophy","volume":"377","author":"Mendell","year":"2017","journal-title":"N Engl J Med"},{"key":"2025080112511347700_awaf074-B16","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1007\/s00415-019-09646-w","article-title":"MRI patterns of muscle involvement in type 2 and 3 spinal muscular atrophy patients","volume":"267","author":"Brogna","year":"2020","journal-title":"J Neurol"},{"key":"2025080112511347700_awaf074-B17","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0960-8966(97)00113-2","article-title":"Segmental distribution of muscle weakness in SMA III: Implications for deterioration in muscle strength with time","volume":"7","author":"Deymeer","year":"1997","journal-title":"Neuromuscul Disord"},{"key":"2025080112511347700_awaf074-B18","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1016\/j.celrep.2016.06.087","article-title":"A stem cell model of the motor circuit uncouples motor neuron death from hyperexcitability induced by SMN deficiency","volume":"16","author":"Simon","year":"2016","journal-title":"Cell Rep"},{"key":"2025080112511347700_awaf074-B19","doi-asserted-by":"crossref","first-page":"2878","DOI":"10.1093\/brain\/awy237","article-title":"UBA1\/GARS-dependent pathways drive sensory-motor connectivity defects in spinal muscular atrophy","volume":"141","author":"Shorrock","year":"2018","journal-title":"Brain"},{"key":"2025080112511347700_awaf074-B20","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.cell.2012.09.011","article-title":"SMN is required for sensory-motor circuit function in Drosophila","volume":"151","author":"Imlach","year":"2012","journal-title":"Cell"},{"key":"2025080112511347700_awaf074-B21","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1093\/jnen\/nly033","article-title":"Glial activation and central synapse loss, but not motoneuron degeneration, are prevented by the sigma-1 receptor agonist PRE-084 in the Smn2B\/\u2212 mouse model of spinal muscular atrophy","volume":"77","author":"Cerver\u00f3","year":"2018","journal-title":"J Neuropathol Exp Neurol"},{"key":"2025080112511347700_awaf074-B22","doi-asserted-by":"crossref","first-page":"e0267990","DOI":"10.1371\/journal.pone.0267990","article-title":"Neuromuscular denervation and deafferentation but not motor neuron death are disease features in the Smn2B\/\u2212 mouse model of SMA","volume":"17","author":"Carlini","year":"2022","journal-title":"PLoS One"},{"key":"2025080112511347700_awaf074-B23","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1093\/hmg\/ddi078","article-title":"SMN\u03947, the major product of the centromeric survival motor neuron (SMN2) gene, extends survival in mice with spinal muscular atrophy and associates with full-length SMN","volume":"14","author":"Le","year":"2005","journal-title":"Hum Mol Genet"},{"key":"2025080112511347700_awaf074-B24","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.cell.2012.09.012","article-title":"An SMN-dependent U12 splicing event essential for motor circuit function","volume":"151","author":"Lotti","year":"2012","journal-title":"Cell"},{"key":"2025080112511347700_awaf074-B25","doi-asserted-by":"crossref","first-page":"3885","DOI":"10.1016\/j.celrep.2019.11.058","article-title":"Stasimon contributes to the loss of sensory synapses and motor neuron death in a mouse model of spinal muscular atrophy","volume":"29","author":"Simon","year":"2019","journal-title":"Cell Rep"},{"key":"2025080112511347700_awaf074-B26","doi-asserted-by":"crossref","first-page":"3767","DOI":"10.1016\/j.celrep.2017.12.003","article-title":"Converging mechanisms of p53 activation drive motor neuron degeneration in spinal muscular atrophy","volume":"21","author":"Simon","year":"2017","journal-title":"Cell Rep"},{"key":"2025080112511347700_awaf074-B27","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1152\/jn.00184.2022","article-title":"In vitro longitudinal lumbar spinal cord preparations to study sensory and recurrent motor microcircuits of juvenile mice","volume":"128","author":"\u00d6zyurt","year":"2022","journal-title":"J Neurophysiol"},{"key":"2025080112511347700_awaf074-B28","doi-asserted-by":"crossref","first-page":"36","DOI":"10.3389\/fnsyn.2019.00036","article-title":"Developmental increase of neocortical presynaptic efficacy via maturation of vesicle replenishment","volume":"11","author":"Bornschein","year":"2019","journal-title":"Front Synaptic Neurosci"},{"key":"2025080112511347700_awaf074-B29","doi-asserted-by":"crossref","first-page":"101236","DOI":"10.1016\/j.xpro.2022.101236","article-title":"Laser microscopy acquisition and analysis of premotor synapses in the murine spinal cord","volume":"3","author":"Buettner","year":"2022","journal-title":"STAR Protoc"},{"key":"2025080112511347700_awaf074-B30","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1093\/hmg\/ddr453","article-title":"Severe neuromuscular denervation of clinically relevant muscles in a mouse model of spinal muscular atrophy","volume":"21","author":"Ling","year":"2012","journal-title":"Hum Mol Genet"},{"key":"2025080112511347700_awaf074-B31","doi-asserted-by":"crossref","first-page":"eabb6871","DOI":"10.1126\/scitranslmed.abb6871","article-title":"Impaired prenatal motor axon development necessitates early therapeutic intervention in severe SMA","volume":"13","author":"Kong","year":"2021","journal-title":"Sci Transl Med"},{"key":"2025080112511347700_awaf074-B32","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1126\/science.1250127","article-title":"Motor neuron disease. SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy","volume":"345","author":"Naryshkin","year":"2014","journal-title":"Science"},{"key":"2025080112511347700_awaf074-B33","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1101\/gad.316059.118","article-title":"Dysregulation of Mdm2 and Mdm4 alternative splicing underlies motor neuron death in spinal muscular atrophy","volume":"32","author":"Van Alstyne","year":"2018","journal-title":"Genes Dev"},{"key":"2025080112511347700_awaf074-B34","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1093\/hmg\/ddw062","article-title":"Pharmacokinetics, pharmacodynamics, and efficacy of a small-molecule SMN2 splicing modifier in mouse models of spinal muscular atrophy","volume":"25","author":"Zhao","year":"2016","journal-title":"Hum Mol Genet"},{"key":"2025080112511347700_awaf074-B35","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s00429-012-0501-7","article-title":"Musculotopic organization of the motor neurons supplying the mouse hindlimb muscles: A quantitative study using fluoro-gold retrograde tracing","volume":"219","author":"B\u00e1cskai","year":"2014","journal-title":"Brain Struct Funct"},{"key":"2025080112511347700_awaf074-B36","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1002\/cne.20987","article-title":"Distribution of vesicular glutamate transporters 1 and 2 in the rat spinal cord, with a note on the spinocervical tract","volume":"497","author":"Persson","year":"2006","journal-title":"J Comp Neurol"},{"key":"2025080112511347700_awaf074-B37","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1038\/nn.3757","article-title":"Gene co-regulation by Fezf2 selects neurotransmitter identity and connectivity of corticospinal neurons","volume":"17","author":"Lodato","year":"2014","journal-title":"Nat Neurosci"},{"key":"2025080112511347700_awaf074-B38","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1146\/annurev.neuro.31.060407.125547","article-title":"Descending pathways in motor control","volume":"31","author":"Lemon","year":"2008","journal-title":"Annu Rev Neurosci"},{"key":"2025080112511347700_awaf074-B39","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1113\/jphysiol.1992.sp019048","article-title":"Corticospinal projections to upper limb motoneurones in humans","volume":"448","author":"Palmer","year":"1992","journal-title":"J Physiol"},{"key":"2025080112511347700_awaf074-B40","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1007\/BF00234119","article-title":"Short-latency subliminal effects of transcranial magnetic stimulation on forearm motoneurones","volume":"96","author":"Baldissera","year":"1993","journal-title":"Exp Brain Res"},{"issue":"Pt 7","key":"2025080112511347700_awaf074-B41","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1093\/brain\/122.7.1327","article-title":"Corticomotoneuronal synaptic connections in normal man: An electrophysiological study","volume":"122","author":"de Noordhout","year":"1999","journal-title":"Brain"},{"key":"2025080112511347700_awaf074-B42","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1002\/ana.26622","article-title":"Multisite Hebbian plasticity restores function in humans with spinal cord injury","volume":"93","author":"Jo","year":"2023","journal-title":"Ann Neurol"},{"key":"2025080112511347700_awaf074-B43","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1007\/s00221-003-1393-9","article-title":"An electron microscopic examination of the corticospinal projection to the cervical spinal cord in the rat: Lack of evidence for cortico-motoneuronal synapses","volume":"149","author":"Yang","year":"2003","journal-title":"Exp Brain Res"},{"key":"2025080112511347700_awaf074-B44","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1126\/science.aan3721","article-title":"Control of species-dependent cortico-motoneuronal connections underlying manual dexterity","volume":"357","author":"Gu","year":"2017","journal-title":"Science"},{"key":"2025080112511347700_awaf074-B45","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1152\/jn.00820.2003","article-title":"Lack of monosynaptic corticomotoneuronal EPSPs in rats: Disynaptic EPSPs mediated via reticulospinal neurons and polysynaptic EPSPs via segmental interneurons","volume":"91","author":"Alstermark","year":"2004","journal-title":"J Neurophysiol"},{"key":"2025080112511347700_awaf074-B46","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/brain\/99.2.235","article-title":"The development of motor control in the rhesus monkey: Evidence concerning the role of corticomotoneuronal connections","volume":"99","author":"Lawrence","year":"1976","journal-title":"Brain"},{"key":"2025080112511347700_awaf074-B47","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1055\/s-0028-1085312","article-title":"Gross and fine motor performance in healthy Swedish children aged fifteen and eighteen months","volume":"10","author":"Lundberg","year":"1979","journal-title":"Neuropadiatrie"},{"key":"2025080112511347700_awaf074-B48","first-page":"295","article-title":"The most common deviations in the development of hand motoricity in children from birth to one year of age","volume":"52","author":"Matijevi\u0107","year":"2013","journal-title":"Acta Clin Croat"},{"key":"2025080112511347700_awaf074-B49","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.neulet.2011.05.005","article-title":"Electrophysiological analysis of the perception of passive movement","volume":"501","author":"Salles","year":"2011","journal-title":"Neurosci Lett"},{"key":"2025080112511347700_awaf074-B50","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1152\/jn.1982.47.3.389","article-title":"Submodality segregation and receptive-field sequences in cuneate, gracile, and external cuneate nuclei of the cat","volume":"47","author":"Dykes","year":"1982","journal-title":"J Neurophysiol"},{"key":"2025080112511347700_awaf074-B51","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/0006-8993(82)90579-0","article-title":"The termination of forelimb nerves in the feline cuneate nucleus demonstrated by the transganglionic transport method","volume":"248","author":"Nyberg","year":"1982","journal-title":"Brain Res"},{"key":"2025080112511347700_awaf074-B52","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/S0370-4475(83)80042-2","article-title":"[Electromyographic study of 50 cases of Werdnig\u2013Hoffmann disease]","volume":"13","author":"Renault","year":"1983","journal-title":"Rev Electroencephalogr Neurophysiol Clin"},{"key":"2025080112511347700_awaf074-B53","doi-asserted-by":"crossref","first-page":"e66","DOI":"10.1212\/CPJ.0000000000000810","article-title":"Transient hyperreflexia: An early diagnostic clue in later-onset spinal muscular atrophy","volume":"10","author":"Oskoui","year":"2020","journal-title":"Neurol Clin Pract"},{"issue":"7s","key":"2025080112511347700_awaf074-B54","doi-asserted-by":"crossref","first-page":"7s23","DOI":"10.1016\/S0929-693X(20)30273-6","article-title":"Clinical features of spinal muscular atrophy (SMA) type 3 (Kugelberg-Welander disease)","volume":"27","author":"Salort-Campana","year":"2020","journal-title":"Arch Pediatr"},{"key":"2025080112511347700_awaf074-B55","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1113\/JP278675","article-title":"Location, location, location: The organization and roles of potassium channels in mammalian motoneurons","volume":"599","author":"Deardorff","year":"2021","journal-title":"J Physiol"},{"issue":"4","key":"2025080112511347700_awaf074-B56","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1038\/s41591-024-03484-8","article-title":"First-in-human study of epidural spinal cord stimulation in individuals with spinal muscular atrophy","volume":"31","author":"Prat-Ortega","year":"2025","journal-title":"Nat Med"},{"issue":"R2","key":"2025080112511347700_awaf074-B57","doi-asserted-by":"crossref","first-page":"R151","DOI":"10.1093\/hmg\/ddx215","article-title":"Spinal muscular atrophy: Antisense oligonucleotide therapy opens the door to an integrated therapeutic landscape","volume":"26","author":"Wood","year":"2017","journal-title":"Hum Mol Genet"},{"key":"2025080112511347700_awaf074-B58","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/nature10485","article-title":"Peripheral SMN restoration is essential for long-term rescue of a severe spinal muscular atrophy mouse model","volume":"478","author":"Hua","year":"2011","journal-title":"Nature"},{"key":"2025080112511347700_awaf074-B59","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/nchembio.1837","article-title":"SMN2 splice modulators enhance U1\u2013pre-mRNA association and rescue SMA mice","volume":"11","author":"Palacino","year":"2015","journal-title":"Nat Chem Biol"},{"key":"2025080112511347700_awaf074-B60","doi-asserted-by":"crossref","first-page":"726468","DOI":"10.3389\/fneur.2021.726468","article-title":"Recombinant adeno-associated virus serotype 9 gene therapy in spinal muscular atrophy","volume":"12","author":"Kotulska","year":"2021","journal-title":"Front Neurol"},{"key":"2025080112511347700_awaf074-B61","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1172\/JCI41615","article-title":"CNS-targeted gene therapy improves survival and motor function in a mouse model of spinal muscular atrophy","volume":"120","author":"Passini","year":"2010","journal-title":"J Clin Invest"},{"key":"2025080112511347700_awaf074-B62","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/S2352-4642(21)00100-0","article-title":"Treatment of infantile-onset spinal muscular atrophy with nusinersen: Final report of a phase 2, open-label, multicentre, dose-escalation study","volume":"5","author":"Finkel","year":"2021","journal-title":"Lancet Child Adolesc Health"},{"key":"2025080112511347700_awaf074-B63","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.nmd.2017.11.004","article-title":"Diagnosis and management of spinal muscular atrophy: Part 2: Pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics","volume":"28","author":"Finkel","year":"2018","journal-title":"Neuromuscul Disord"},{"key":"2025080112511347700_awaf074-B64","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1001\/jamaneurol.2021.1272","article-title":"Five-year extension results of the Phase 1 START trial of Onasemnogene Abeparvovec in spinal muscular atrophy","volume":"78","author":"Mendell","year":"2021","journal-title":"JAMA Neurol"},{"key":"2025080112511347700_awaf074-B65","doi-asserted-by":"crossref","first-page":"417","DOI":"10.3390\/cells11030417","article-title":"Restoring SMN expression: An overview of the therapeutic developments for the treatment of spinal muscular atrophy","volume":"11","author":"Aslesh","year":"2022","journal-title":"Cells"},{"key":"2025080112511347700_awaf074-B66","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.nmd.2019.09.007","article-title":"Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study","volume":"29","author":"De Vivo","year":"2019","journal-title":"Neuromuscul Disord"},{"key":"2025080112511347700_awaf074-B67","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.tins.2020.11.009","article-title":"Spinal muscular atrophy: In the challenge lies a solution","volume":"44","author":"Wirth","year":"2021","journal-title":"Trends Neurosci"},{"key":"2025080112511347700_awaf074-B68","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41434-022-00349-y","article-title":"Curing SMA: Are we there yet?","volume":"30","author":"Reilly","year":"2023","journal-title":"Gene Ther"},{"key":"2025080112511347700_awaf074-B69","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/s41582-020-00413-4","article-title":"Spinal muscular atrophy \u2013 insights and challenges in the treatment era","volume":"16","author":"Mercuri","year":"2020","journal-title":"Nat Rev Neurol"},{"key":"2025080112511347700_awaf074-B70","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1038\/s41591-022-01866-4","article-title":"Onasemnogene abeparvovec for presymptomatic infants with two copies of SMN2 at risk for spinal muscular atrophy type 1: The Phase III SPR1NT trial","volume":"28","author":"Strauss","year":"2022","journal-title":"Nat Med"},{"key":"2025080112511347700_awaf074-B71","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1038\/s41591-022-01867-3","article-title":"Onasemnogene abeparvovec for presymptomatic infants with three copies of SMN2 at risk for spinal muscular atrophy: The Phase III SPR1NT trial","volume":"28","author":"Strauss","year":"2022","journal-title":"Nat Med"},{"key":"2025080112511347700_awaf074-B72","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1186\/s12887-022-03671-x","article-title":"Advances and limitations for the treatment of spinal muscular atrophy","volume":"22","author":"Day","year":"2022","journal-title":"BMC Pediatr"},{"key":"2025080112511347700_awaf074-B73","doi-asserted-by":"crossref","first-page":"100878","DOI":"10.1016\/j.spen.2021.100878","article-title":"Spinal muscular atrophy","volume":"37","author":"Nicolau","year":"2021","journal-title":"Semin Pediatr Neurol"},{"key":"2025080112511347700_awaf074-B74","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1007\/s00415-023-11560-1","article-title":"Two-year efficacy and safety of risdiplam in patients with type 2 or non-ambulant type 3 spinal muscular atrophy (SMA)","volume":"270","author":"Oskoui","year":"2023","journal-title":"J Neurol"},{"key":"2025080112511347700_awaf074-B75","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1038\/s41593-021-00827-3","article-title":"Gain of toxic function by long-term AAV9-mediated SMN overexpression in the sensorimotor circuit","volume":"24","author":"Van Alstyne","year":"2021","journal-title":"Nat Neurosci"},{"key":"2025080112511347700_awaf074-B76","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s00421-002-0577-5","article-title":"Considerations for use of the Hoffmann reflex in exercise studies","volume":"86","author":"Zehr","year":"2002","journal-title":"Eur J Appl Physiol"},{"key":"2025080112511347700_awaf074-B77","doi-asserted-by":"crossref","first-page":"1206552","DOI":"10.3389\/fendo.2023.1206552","article-title":"Evidence of impaired H-reflex and H-reflex rate-dependent depression in diabetes, prediabetes and obesity: A mini-review","volume":"14","author":"Kababie-Ameo","year":"2023","journal-title":"Front Endocrinol (Lausanne)"}],"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awaf074\/62048449\/awaf074.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/article-pdf\/148\/8\/2797\/62048449\/awaf074.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/article-pdf\/148\/8\/2797\/62048449\/awaf074.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T16:51:29Z","timestamp":1754067089000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/article\/148\/8\/2797\/8029810"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,21]]},"references-count":77,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,2,21]]},"published-print":{"date-parts":[[2025,8,1]]}},"URL":"https:\/\/doi.org\/10.1093\/brain\/awaf074","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.06.03.24308132","asserted-by":"object"}]},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,8]]},"published":{"date-parts":[[2025,2,21]]}}}