{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T02:26:12Z","timestamp":1773714372741,"version":"3.50.1"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T00:00:00Z","timestamp":1671494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["Ciencia B\u00e1sica A1-S-8686"],"award-info":[{"award-number":["Ciencia B\u00e1sica A1-S-8686"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006087","name":"Direcci\u00f3n General de Asuntos del Personal Acad\u00e9mico, Universidad Nacional Aut\u00f3noma de M\u00e9xico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006087","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006087","name":"Direcci\u00f3n General de Asuntos del Personal Acad\u00e9mico, Universidad Nacional Aut\u00f3noma de M\u00e9xico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006087","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Pyramidal tract neurons (PTNs) are fundamental elements for motor control. However, it is largely unknown if PTNs are segregated into different subtypes with distinct characteristics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using anatomical and electrophysiological tools, we analyzed in mice motor cortex PTNs projecting to red and pontine midbrain nuclei, which are important hubs connecting cerebral cortex and cerebellum playing a critical role in the regulation of movement.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We reveal that the vast majority of M1 neurons projecting to the red and pontine nuclei constitutes different populations. Corticopontine neurons have higher conduction velocities and morphologically, a most homogeneous dendritic and spine distributions along cortical layers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The results indicate that cortical neurons projecting to the red and pontine nuclei constitute distinct anatomical and functional pathways which may contribute differently to sensorimotor integration.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fncel.2022.1073731","type":"journal-article","created":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T05:53:30Z","timestamp":1671515610000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Different subtypes of motor cortex pyramidal tract neurons projects to red and pontine nuclei"],"prefix":"10.3389","volume":"16","author":[{"given":"Veronica","family":"Lopez-Virgen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"Olivares-Moreno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor","family":"de Lafuente","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Concha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerardo","family":"Rojas-Piloni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/0006-8993(92)91629-s","article-title":"Origins and collateralization of corticospinal, corticopontine, corticorubral and corticostriatal tracts: a multiple retrograde fluorescent tracing study.","volume":"586","author":"Akintunde","year":"1992","journal-title":"Brain Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1038\/2081002a0","article-title":"Cerebello-rubral connexions in the cat.","volume":"208","author":"Angaut","year":"1965","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1007\/s00429-020-02171-x","article-title":"Red nucleus structure and function: from anatomy to clinical neurosciences.","volume":"226","author":"Basile","year":"2021","journal-title":"Brain Struct. Funct."},{"key":"B4","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1113\/jphysiol.1985.sp015720","article-title":"Activity dependence of action potential duration in rat supraoptic neurosecretory neurones recorded in vitro.","volume":"363","author":"Bourque","year":"1985","journal-title":"J. Physiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1016\/B978-0-12-385157-4.01173-8","article-title":"Pontine nuclei","author":"Brodal","year":"2014","journal-title":"Encyclopedia of the Neurological Sciences (Second Edition)"},{"key":"B6","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/0168-0102(92)90092-Q","article-title":"Organization of the pontine nuclei.","volume":"13","author":"Brodal","year":"1992","journal-title":"Neurosci. Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/cne.901760102","article-title":"A study of afferent input to the inferior olivary complex in the rat by retrograde axonal transport of horseradish peroxidase.","volume":"176","author":"Brown","year":"1977","journal-title":"J. Comp. Neurol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/0304-3940(79)91477-0","article-title":"Cells of origin of the frontal projections to magnocellular and parvocellular red nucleus and superior colliculus in cynomolgus monkey. An HRP study.","volume":"12","author":"Catman-Berrevoets","year":"1979","journal-title":"Neurosci. Lett."},{"key":"B9","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1007\/BF00236713","article-title":"Somatotopical organization of the projection from the nucleus interpositus anterior of the cerebellum to the red nucleus. An experimental study in the cat with silver impregnation methods.","volume":"2","author":"Courville","year":"1966","journal-title":"Exp. Brain Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/0166-4328(88)90078-2","article-title":"Topographic organization of the interpositorubral connections in the rat. A WGA-HRP study.","volume":"28","author":"Daniel","year":"1988","journal-title":"Behav. Brain Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1038\/s41586-018-0642-9","article-title":"Distinct descending motor cortex pathways and their roles in movement.","volume":"563","author":"Economo","year":"2018","journal-title":"Nature"},{"key":"B12","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/0006-8993(72)90170-9","article-title":"The ascending and descending projections of the red nucleus in the cat: an experimental study using an autoradiographic tracing method.","volume":"48","author":"Edwards","year":"1972","journal-title":"Brain Res."},{"key":"B13","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1093\/cercor\/bhp152","article-title":"Cell-type specific properties of pyramidal neurons in neocortex underlying a layout that is modifiable depending on the cortical area.","volume":"20","author":"Groh","year":"2010","journal-title":"Cereb. Cortex"},{"key":"B14","first-page":"1","article-title":"The red nucleus: past, present, and future.","volume":"9","author":"Gruber","year":"2010","journal-title":"Neuroanatomy"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-03000-8","article-title":"Single-axon level morphological analysis of corticofugal projection neurons in mouse barrel field.","volume":"7","author":"Guo","year":"2017","journal-title":"Sci. Rep."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.65906","article-title":"Disrupting cortico-cerebellar communication impairs dexterity","volume":"10","author":"Guo","year":"2021","journal-title":"ELife"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.00400","article-title":"Convergence of pontine and proprioceptive streams onto multimodal cerebellar granule cells.","volume":"2","author":"Huang","year":"2013","journal-title":"Elife"},{"key":"B18","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/0006-8993(76)90217-1","article-title":"Cells of origin of corticorubral projections from the arm area of primate motor cortex and their synaptic actions in the red nucleus.","volume":"110","author":"Humphrey","year":"1976","journal-title":"Brain Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.ymeth.2015.01.005","article-title":"Robust methods to create ex vivo minimum deformation atlases for brain mapping.","volume":"73","author":"Janke","year":"2015","journal-title":"Methods"},{"key":"B20","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1002\/cne.901020304","article-title":"On the efferent fibers of the cerebellar nuclei in the cat.","volume":"102","author":"Jansen","year":"1955","journal-title":"J. Comp. Neurol."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-64665-2","article-title":"Anatomically revealed morphological patterns of pyramidal neurons in layer 5 of the motor cortex.","volume":"10","author":"Jiang","year":"2020","journal-title":"Sci. Rep."},{"key":"B22","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1016\/0166-2236(90)90079-p","article-title":"Corticospinal, rubrospinal and rubro-olivary projections: a unifying hypothesis.","volume":"13","author":"Kennedy","year":"1990","journal-title":"Trends Neurosci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1016\/j.neuron.2015.11.002","article-title":"Three types of cortical layer 5 neurons that differ in brain-wide connectivity and function.","volume":"88","author":"Kim","year":"2015","journal-title":"Neuron"},{"key":"B24","doi-asserted-by":"publisher","first-page":"5990","DOI":"10.1523\/JNEUROSCI.5717-11.2012","article-title":"The subthalamic nucleus is one of multiple innervation sites for long-range corticofugal axons: a single-axon tracing study in the rat.","volume":"32","author":"Kita","year":"2012","journal-title":"J. Neurosci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"3403","DOI":"10.1093\/cercor\/bhz318","article-title":"Slowly-conducting pyramidal tract neurons in macaque and rat.","volume":"30","author":"Kraskov","year":"2020","journal-title":"Cereb. Cortex."},{"key":"B26","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1038\/18686","article-title":"A new cellular mechanism for coupling inputs arriving at different cortical layers.","volume":"398","author":"Larkum","year":"1999","journal-title":"Nature"},{"key":"B27","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.brainres.2016.01.006","article-title":"Cortical projections to the red nucleus and the brain stem in the rhesus monkey.","volume":"1645","author":"Lemon","year":"2016","journal-title":"Brain Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1007\/s00429-011-0348-3","article-title":"The red nucleus and the rubrospinal projection in the mouse.","volume":"217","author":"Liang","year":"2012","journal-title":"Brain Struct. Funct."},{"key":"B29","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1152\/physrev.1967.47.3.383","article-title":"The mammalian red nucleus.","volume":"47","author":"Massion","year":"1967","journal-title":"Physiol. Rev."},{"key":"B30","doi-asserted-by":"publisher","first-page":"2439","DOI":"10.1089\/neu.2010.1708","article-title":"Impaired arpeggio movement in skilled reaching by rubrospinal tract lesions in the rat: a behavioral\/anatomical fractionation.","volume":"28","author":"Morris","year":"2011","journal-title":"J. Neurotrauma"},{"key":"B31","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.neuroscience.2015.03.027","article-title":"The differential contributions of the parvocellular and the magnocellular subdivisions of the red nucleus to skilled reaching in the rat.","volume":"295","author":"Morris","year":"2015","journal-title":"Neuroscience"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3791\/51359","article-title":"Juxtasomal biocytin labeling to study the structure-function relationship of individual cortical neurons.","volume":"84","author":"Narayanan","year":"2014","journal-title":"J. Vis. Exp."},{"key":"B33","doi-asserted-by":"publisher","first-page":"4450","DOI":"10.1093\/cercor\/bhv053","article-title":"Beyond columnar organization: cell type- and target layer-specific principles of horizontal axon projection patterns in rat vibrissal cortex.","volume":"25","author":"Narayanan","year":"2015","journal-title":"Cereb. Cortex"},{"key":"B34","doi-asserted-by":"publisher","first-page":"4188","DOI":"10.1073\/pnas.1100647108","article-title":"Three-dimensional axon morphologies of individual layer 5 neurons indicate cell type-specific intracortical pathways for whisker motion and touch.","volume":"108","author":"Oberlaender","year":"2011","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1117\/1.2815693","article-title":"Transmitted light brightfield mosaic microscopy for three-dimensional tracing of single neuron morphology.","volume":"12","author":"Oberlaender","year":"2007","journal-title":"J. Biomed. Opt."},{"key":"B36","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1038\/nature13186","article-title":"A mesoscale connectome of the mouse brain.","volume":"508","author":"Oh","year":"2014","journal-title":"Nature"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1186\/s12868-019-0533-5","article-title":"Mouse corticospinal system comprises different functional neuronal ensembles depending on their hodology.","volume":"20","author":"Olivares-Moreno","year":"2019","journal-title":"BMC Neurosci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"3945","DOI":"10.1007\/s00429-017-1447-6","article-title":"The rat corticospinal system is functionally and anatomically segregated.","volume":"222","author":"Olivares-Moreno","year":"2017","journal-title":"Brain Struct. Funct."},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.686481","article-title":"Corticospinal vs rubrospinal revisited: an evolutionary perspective for sensorimotor integration.","volume":"15","author":"Olivares-Moreno","year":"2021","journal-title":"Front. Neurosci."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2013.00174","article-title":"Diversity of layer 5 projection neurons in the mouse motor cortex.","volume":"7","author":"Oswald","year":"2013","journal-title":"Front. Cell. Neurosci."},{"key":"B41","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/0165-0270(95)00144-1","article-title":"A novel single-cell staining procedure performed in vivo under electrophysiological control: morpho-functional features of juxtacellularly labeled thalamic cells and other central neurons with biocytin or Neurobiotin.","volume":"65","author":"Pinault","year":"1996","journal-title":"J. Neurosci. Methods"},{"key":"B42","doi-asserted-by":"publisher","first-page":"5120","DOI":"10.1523\/JNEUROSCI.0002-12.2012","article-title":"Axonal thinning and extensive remyelination without chronic demyelination in spinal injured rats.","volume":"32","author":"Powers","year":"2012","journal-title":"J. Neurosci."},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00233","article-title":"Anatomy and physiology of the thick-tufted layer 5 pyramidal neuron.","volume":"9","author":"Ramaswamy","year":"2015","journal-title":"Front. Cell. Neurosci."},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00971-0","article-title":"Relationships between structure, in vivo function and long-range axonal target of cortical pyramidal tract neurons.","volume":"8","author":"Rojas-Piloni","year":"2017","journal-title":"Nat. Commun."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1093\/brain\/awh138","article-title":"The human basis pontis: motor syndromes and topographic organization.","volume":"127","author":"Schmahmann","year":"2004","journal-title":"Brain"},{"key":"B46","doi-asserted-by":"publisher","first-page":"3475","DOI":"10.1523\/JNEUROSCI.15-05-03475.1995","article-title":"Modular organization of the pontine nuclei: dendritic fields of identified pontine projection neurons in the rat respect the borders of cortical afferent fields.","volume":"15","author":"Schwarz","year":"1995","journal-title":"J. Neurosci."},{"key":"B47","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/B978-0-12-369497-3.10011-1","article-title":"Chapter 11 - Cerebellum","author":"Sillitoe","year":"2012","journal-title":"The Mouse Nervous System"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0038482","article-title":"Action potential waveform variability limits multi-unit separation in freely behaving rats.","volume":"7","author":"Stratton","year":"2012","journal-title":"PLoS One"},{"key":"B49","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.neures.2004.02.001","article-title":"Conduction properties of identified neural pathways in the central nervous system of mice in vivo.","volume":"49","author":"Tanaka","year":"2004","journal-title":"Neurosci. Res."},{"key":"B50","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1126\/science.1249766","article-title":"Distinct profiles of myelin distribution along single axons of pyramidal neurons in the neocortex.","volume":"344","author":"Tomassy","year":"2014","journal-title":"Science"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.116137","article-title":"MRtrix3: a fast, flexible and open software framework for medical image processing and visualisation.","volume":"202","author":"Tournier","year":"2019","journal-title":"Neuroimage"},{"key":"B52","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/0014-4886(70)90065-8","article-title":"Extracellular microelectrode sampling bias.","volume":"29","author":"Towe","year":"1970","journal-title":"Exp. Neurol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"6154","DOI":"10.1523\/JNEUROSCI.0581-09.2009","article-title":"The role of the monkey dorsal pontine nuclei in goal-directed eye and hand movements.","volume":"29","author":"Tziridis","year":"2009","journal-title":"J. Neurosci."},{"key":"B54","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1002\/cne.23678","article-title":"Development of MRI-based atlases of non-human brains.","volume":"523","author":"Ullmann","year":"2015","journal-title":"J. Comp. Neurol."},{"key":"B55","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S0361-9230(99)00229-4","article-title":"Recent techniques for tracing pathways in the central nervous system of developing and adult mammals.","volume":"51","author":"Vercelli","year":"2000","journal-title":"Brain Res. Bull."},{"key":"B56","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1016\/j.cell.2019.02.019","article-title":"Shared cortex-cerebellum dynamics in the execution and learning of a motor task.","volume":"177","author":"Wagner","year":"2019","journal-title":"Cell"},{"key":"B57","doi-asserted-by":"publisher","first-page":"2379","DOI":"10.1016\/0306-4522(81)90024-5","article-title":"A re-examination of the rubro-olivary tract in the cat, using horseradish peroxidase as a retrograde and an anterograde neuronal tracer.","volume":"6","author":"Walberg","year":"1981","journal-title":"Neuroscience"},{"key":"B58","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1016\/j.cell.2020.04.007","article-title":"The Allen mouse brain common coordinate framework: a 3D reference atlas.","volume":"181","author":"Wang","year":"2020","journal-title":"Cell"},{"key":"B59","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/s0166-4328(97)00152-6","article-title":"Paw and limb use in skilled and spontaneous reaching after pyramidal tract, red nucleus and combined lesions in the rat: behavioral and anatomical dissociations.","volume":"93","author":"Whishaw","year":"1998","journal-title":"Behav. Brain Res."},{"key":"B60","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/0166-4328(90)90005-Y","article-title":"Red nucleus lesions do not affect limb preference or use, but exacerbate the effects of motor cortex lesions on grasping in the rat.","volume":"40","author":"Whishaw","year":"1990","journal-title":"Behav. Brain Res."},{"key":"B61","doi-asserted-by":"publisher","first-page":"2265","DOI":"10.1093\/cercor\/bhq068","article-title":"Dimensions of a projection column and architecture of VPM and POm axons in rat vibrissal cortex.","volume":"20","author":"Wimmer","year":"2010","journal-title":"Cereb. Cortex"},{"key":"B62","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1016\/j.cell.2019.07.042","article-title":"Reconstruction of 1,000 projection neurons reveals new cell types and organization of long-range connectivity in the mouse brain.","volume":"179","author":"Winnubst","year":"2019","journal-title":"Cell"}],"container-title":["Frontiers in Cellular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2022.1073731\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T05:53:38Z","timestamp":1671515618000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2022.1073731\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,20]]},"references-count":62,"alternative-id":["10.3389\/fncel.2022.1073731"],"URL":"https:\/\/doi.org\/10.3389\/fncel.2022.1073731","relation":{},"ISSN":["1662-5102"],"issn-type":[{"value":"1662-5102","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,20]]},"article-number":"1073731"}}