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C boutons characteristically display a postsynaptic specialization consisting of an endoplasmic reticulum\u2010related subsurface cistern (SSC) of unknown function. In the present work, by using confocal microscopy and ultrastructural immunolabeling, we demonstrate that neuregulin\u20101 (NRG1) accumulates in the SSC of mouse spinal MNs. We also show that the NRG1 receptors erbB2 and erbB4 are presynaptically localized within C boutons, suggesting that NRG1\u2010based retrograde signaling may occur in this type of synapse. In most of the cranial nuclei, MNs display the same pattern of NRG1 distribution as that observed in spinal cord MNs. Conversely, MNs in oculomotor nuclei, which are spared in amyotrophic lateral sclerosis (ALS), lack both C boutons and SSC\u2010associated NRG1. NRG1 in spinal MNs is developmentally regulated and depends on the maintenance of nerve\u2010muscle interactions, as we show after nerve transection experiments. Changes in NRG1 in C boutons were also investigated in mouse models of MN diseases:\n                    <jats:italic>i.e.<\/jats:italic>\n                    , spinal muscular atrophy (SMN\u03947) and ALS (SOD1\n                    <jats:sup>G93A<\/jats:sup>\n                    ). In both models, a transient increase in NRG1 in C boutons occurs during disease progression. These data increase our understanding of the role of C boutons in MN physiology and pathology.\u2014Gallart\u2010Palau, X., Tarabal, O., Casanovas, A., S\u00e1bado, J., Correa, F. J., Hereu, M., Piedrafita, L., Calder\u00f3, J., Esquerda, J. E. Neuregulin\u20101 is concentrated in the postsynaptic subsurface cistern of C\u2010bouton inputs to \u03b1\u2010motoneurons and altered during motoneuron diseases.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    28, 3618\u20133632 (2014).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.13-248583","type":"journal-article","created":{"date-parts":[[2014,5,7]],"date-time":"2014-05-07T00:35:43Z","timestamp":1399422943000},"page":"3618-3632","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Neuregulin\u20101 is concentrated in the postsynaptic subsurface cistern of C\u2010bouton inputs to \u03b1\u2010motoneurons and altered during motoneuron diseases"],"prefix":"10.1096","volume":"28","author":[{"given":"Xavier","family":"Gallart\u2010Palau","sequence":"first","affiliation":[{"name":"Unitat de Neurobiologia Cellular, Departament de Medicina Experimental, Facultat de Medicina Institut de Recerca Biom\u00e8dica de Lleida (IRBLLEIDA), Universitat de Lleida Lleida Catalonia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Tarabal","sequence":"additional","affiliation":[{"name":"Unitat de Neurobiologia Cellular, Departament de Medicina Experimental, Facultat de Medicina Institut de Recerca Biom\u00e8dica de Lleida (IRBLLEIDA), Universitat de Lleida Lleida Catalonia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Casanovas","sequence":"additional","affiliation":[{"name":"Unitat de Neurobiologia Cellular, Departament de Medicina Experimental, Facultat de Medicina Institut de Recerca Biom\u00e8dica de Lleida (IRBLLEIDA), Universitat de Lleida Lleida Catalonia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"S\u00e1bado","sequence":"additional","affiliation":[{"name":"Unitat de Neurobiologia Cellular, Departament de Medicina Experimental, Facultat de Medicina Institut de Recerca Biom\u00e8dica de Lleida (IRBLLEIDA), Universitat de Lleida Lleida Catalonia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco J.","family":"Correa","sequence":"additional","affiliation":[{"name":"Unitat de Neurobiologia Cellular, Departament de Medicina Experimental, Facultat de Medicina Institut de Recerca Biom\u00e8dica de Lleida (IRBLLEIDA), Universitat de Lleida Lleida Catalonia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Hereu","sequence":"additional","affiliation":[{"name":"Unitat de Neurobiologia Cellular, Departament de Medicina Experimental, Facultat de Medicina Institut de Recerca Biom\u00e8dica de Lleida (IRBLLEIDA), Universitat de Lleida Lleida Catalonia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00eddia","family":"Piedrafita","sequence":"additional","affiliation":[{"name":"Unitat de Neurobiologia Cellular, Departament de Medicina Experimental, Facultat de Medicina Institut de Recerca Biom\u00e8dica de Lleida (IRBLLEIDA), Universitat de Lleida Lleida Catalonia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Calder\u00f3","sequence":"additional","affiliation":[{"name":"Unitat de Neurobiologia Cellular, Departament de Medicina Experimental, Facultat de Medicina Institut de Recerca Biom\u00e8dica de Lleida (IRBLLEIDA), Universitat de Lleida Lleida Catalonia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep E.","family":"Esquerda","sequence":"additional","affiliation":[{"name":"Unitat de Neurobiologia Cellular, Departament de Medicina Experimental, Facultat de Medicina Institut de Recerca Biom\u00e8dica de Lleida (IRBLLEIDA), Universitat de Lleida Lleida Catalonia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,5,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2000.80.2.767"},{"key":"e_1_2_7_3_1","first-page":"49","article-title":"Ultrastructure and distribution of neuronal and glial elements on the surface of the proximal part of a motoneuron dendrite, as analyzed by serial sections","volume":"332","author":"Conradi S.","year":"1969","journal-title":"Acta Physiol. 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