{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:53:43Z","timestamp":1790787223065,"version":"4.1.0"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neural Circuits"],"abstract":"<jats:p>The cerebellar output can trigger whisker movement through indirect projections that pass via several brainstem pre-motor nuclei before reaching the facial nucleus, which directly controls whisker movements in rodents. Although the central pattern generator function of the intermediate reticular formation has been recently clarified, the roles of the other whisker pre-motor nuclei remain unclear. Here, we set out to compare the whisker movement kinematics of the main pre-motor whisker nuclei connecting the cerebellum and the facial nucleus. We optogenetically stimulated neurons located in the cerebellar cortex: Purkinje cells (PCs), the cerebellar nuclei (CN), the red nucleus (RN), the superior colliculus (SC), the spinal trigeminal nucleus (SV), and the reticular formation (RF); in head-fixed awake mice while monitoring the bilateral whisker movement. We show that optogenetic stimulation of the RN, SC, and SV resulted in a predominant midpoint change, whereas optogenetic stimulation of the PCs, CN, and RF resulted in faster whisker movements. In addition, the excitation of PCs, the RN, and SC resulted in symmetric bilateral whisking. In contrast, the excitation of the RF, and SV resulted in initial asymmetric movement, followed by a more dominantly symmetrical bilateral whisking. Importantly, PC excitation generated a robust rhythmic whisking pattern that could not be reproduced by direct CN stimulation, indicating that the cerebellar cortex sculpts CN population output rather than simply gating it. Our results suggest that cerebellar output engages multiple, specialized pre-motor pathways through a divergent-convergent architecture. This system allows different pre-motor nuclei to modulate distinct aspects of whisking kinematics, ultimately shaping whisker motor dynamics.<\/jats:p>","DOI":"10.3389\/fncir.2025.1706704","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T06:51:56Z","timestamp":1769064716000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The cerebellum engages multiple pre-motor pathways through a divergent-convergent architecture to shape whisker dynamics"],"prefix":"10.3389","volume":"19","author":[{"given":"Staf","family":"Bauer","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Erasmus MC","place":["Rotterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peipei","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Erasmus MC","place":["Rotterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"van Wingerden","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Erasmus MC","place":["Rotterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hehe","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Erasmus MC","place":["Rotterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Romano","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Erasmus MC","place":["Rotterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.neuroscience.2017.04.004","article-title":"Optogenetic stimulation of cortex to map evoked whisker movements in awake head-restrained mice.","volume":"368","author":"Auffret","year":"2018","journal-title":"Neuroscience"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1831","DOI":"10.3390\/biomedicines10081831","article-title":"Purkinje cell activity resonation generates rhythmic behaviors at the preferred frequency of 8 Hz.","volume":"10","author":"Bauer","year":"2022","journal-title":"Biomedicines"},{"key":"B4","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1016\/j.neuron.2017.07.022","article-title":"Parallel inhibitory and excitatory trigemino-facial feedback circuitry for reflexive vibrissa movement.","volume":"95","author":"Bellavance","year":"2017","journal-title":"Neuron"},{"key":"B5","doi-asserted-by":"publisher","first-page":"588445","DOI":"10.3389\/fncel.2020.588445","article-title":"WhiskEras: A new algorithm for accurate whisker tracking.","volume":"14","author":"Betting","year":"2020","journal-title":"Front. Cell. Neurosci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"53","DOI":"10.3389\/fnint.2011.00053","article-title":"Anatomical pathways involved in generating and sensing rhythmic whisker movements.","volume":"5","author":"Bosman","year":"2011","journal-title":"Front. Integr. Neurosci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"e10509","DOI":"10.7554\/eLife.10509","article-title":"The cerebellum linearly encodes whisker position during voluntary movement.","volume":"5","author":"Chen","year":"2016","journal-title":"eLife"},{"key":"B8","doi-asserted-by":"publisher","first-page":"3029","DOI":"10.1016\/j.cub.2019.07.068","article-title":"The sensorimotor basis of whisker-guided anteroposterior object localization in head-fixed mice.","volume":"29","author":"Cheung","year":"2019","journal-title":"Curr. Biol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1016\/j.neuron.2011.02.022","article-title":"Synaptic mechanisms underlying sparse coding of active touch.","volume":"69","author":"Crochet","year":"2011","journal-title":"Neuron"},{"key":"B10","doi-asserted-by":"publisher","first-page":"e2204155119","DOI":"10.1073\/pnas.2204155119","article-title":"Time and tide of cerebellar synchrony.","volume":"119","author":"De Zeeuw","year":"2022","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B11","doi-asserted-by":"publisher","first-page":"7493048","DOI":"10.1155\/2016\/7493048","article-title":"Circuits in the ventral medulla that phase-lock motoneurons for coordinated sniffing and whisking.","volume":"2016","author":"Deschenes","year":"","journal-title":"Neural Plast."},{"key":"B12","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.neuron.2016.03.007","article-title":"Inhibition, not excitation, drives rhythmic whisking.","volume":"90","author":"Deschenes","year":"","journal-title":"Neuron"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1152\/jn.1984.51.6.1196","article-title":"Electrophysiology of neurons of lateral thalamic nuclei in cat - resting properties and burst discharges.","volume":"51","author":"Deschenes","year":"1984","journal-title":"J. Neurophysiol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"9818","DOI":"10.1523\/JNEUROSCI.1809-19.2019","article-title":"Whisking asymmetry signals motor preparation and the behavioral state of mice.","volume":"39","author":"Dominiak","year":"2019","journal-title":"J. Neurosci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"83","DOI":"10.3758\/s13428-012-0225-x","article-title":"Assessing bimodality to detect the presence of a dual cognitive process.","volume":"45","author":"Freeman","year":"2013","journal-title":"Behav. Res. Methods"},{"key":"B16","doi-asserted-by":"publisher","first-page":"5165","DOI":"10.1113\/Jp281510","article-title":"Silences, spikes and bursts: Three-part knot of the neural code.","volume":"601","author":"Friedenberger","year":"2023","journal-title":"J. Physiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"3833","DOI":"10.1016\/j.neuron.2022.08.020","article-title":"Theory of hierarchically organized neuronal oscillator dynamics that mediate rodent rhythmic whisking.","volume":"110","author":"Golomb","year":"2022","journal-title":"Neuron"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1038\/s41593-020-0701-z","article-title":"Climbing fiber synapses rapidly and transiently inhibit neighboring Purkinje cells via ephaptic coupling.","volume":"23","author":"Han","year":"2020","journal-title":"Nat. Neurosci."},{"key":"B19","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1002\/cne.10089","article-title":"Functional circuitry involved in the regulation of whisker movements.","volume":"442","author":"Hattox","year":"2002","journal-title":"J. Comp. Neurol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2321","DOI":"10.1523\/JNEUROSCI.4547-13.2014","article-title":"Precise control of movement kinematics by optogenetic inhibition of Purkinje cell activity.","volume":"34","author":"Heiney","year":"2014","journal-title":"J. Neurosci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1152\/jn.90478.2008","article-title":"Superior colliculus control of vibrissa movements.","volume":"100","author":"Hemelt","year":"2008","journal-title":"J. Neurophysiol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"3438","DOI":"10.1523\/JNEUROSCI.5008-07.2008","article-title":"Biomechanics of the vibrissa motor plant in rat: Rhythmic whisking consists of triphasic neuromuscular activity.","volume":"28","author":"Hill","year":"2008","journal-title":"J. Neurosci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/j.neuron.2011.09.020","article-title":"Primary motor cortex reports efferent control of vibrissa motion on multiple timescales.","volume":"72","author":"Hill","year":"2011","journal-title":"Neuron"},{"key":"B24","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1007\/BF00236312","article-title":"Difference in projections to the lateral and medial facial nucleus: Anatomically separate pathways for rhythmical vibrissa movement in rats.","volume":"65","author":"Isokawa-Akesson","year":"1987","journal-title":"Exp. Brain Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"781","DOI":"10.2170\/jjphysiol.34.781","article-title":"The modifiable neuronal network of the cerebellum.","volume":"34","author":"Ito","year":"1984","journal-title":"Jpn. J. Physiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1152\/physrev.2001.81.3.1143","article-title":"Cerebellar long-term depression: Characterization, signal transduction, and functional roles.","volume":"81","author":"Ito","year":"2001","journal-title":"Physiol. Rev."},{"key":"B27","doi-asserted-by":"publisher","first-page":"100","DOI":"10.3389\/fncir.2018.00100","article-title":"A descending circuit derived from the superior colliculus modulates vibrissal movements.","volume":"12","author":"Kaneshige","year":"2018","journal-title":"Front. Neural Circuits"},{"key":"B28","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/j.conb.2006.06.009","article-title":"Active sensation: Insights from the rodent vibrissa sensorimotor system.","volume":"16","author":"Kleinfeld","year":"2006","journal-title":"Curr. Opin. Neurobiol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1038\/nn.3693","article-title":"More than a rhythm of life: Breathing as a binder of orofacial sensation.","volume":"17","author":"Kleinfeld","year":"2014","journal-title":"Nat. Neurosci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1016\/j.cub.2017.01.013","article-title":"Coordination of orofacial motor actions into exploratory behavior by rat.","volume":"27","author":"Kurnikova","year":"2017","journal-title":"Curr. Biol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1113\/jphysiol.2005.102764","article-title":"Olivocerebellar modulation of motor cortex ability to generate vibrissal movements in rat.","volume":"571","author":"Lang","year":"2006","journal-title":"J. Physiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1016\/j.neuron.2015.03.010","article-title":"Circuit mechanisms underlying motor memory formation in the cerebellum.","volume":"86","author":"Lee","year":"2015","journal-title":"Neuron"},{"key":"B33","doi-asserted-by":"publisher","first-page":"e2015292118","DOI":"10.1073\/pnas.2015292118","article-title":"Cerebellar Purkinje cells can differentially modulate coherence between sensory and motor cortex depending on region and behavior.","volume":"118","author":"Lindeman","year":"2021","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B34","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1002\/cne.23724","article-title":"Feedback in the brainstem: An excitatory disynaptic pathway for control of whisking.","volume":"523","author":"Matthews","year":"2015","journal-title":"J. Comp. Neurol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/S0079-6123(05)51011-2","article-title":"The mammalian superior colliculus: Laminar structure and connections.","volume":"151","author":"May","year":"2006","journal-title":"Prog. Brain Res."},{"key":"B36","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1038\/nature12076","article-title":"Hierarchy of orofacial rhythms revealed through whisking and breathing.","volume":"497","author":"Moore","year":"2013","journal-title":"Nature"},{"key":"B37","doi-asserted-by":"publisher","first-page":"e1006475","DOI":"10.1371\/journal.pcbi.1006475","article-title":"Quasiperiodic rhythms of the inferior olive.","volume":"15","author":"Negrello","year":"2019","journal-title":"PLoS Comput. Biol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1007\/s12311-022-01499-w","article-title":"A Systematic review of direct outputs from the cerebellum to the brainstem and diencephalon in mammals.","volume":"23","author":"Novello","year":"2022","journal-title":"Cerebellum"},{"key":"B39","doi-asserted-by":"publisher","first-page":"2137","DOI":"10.1152\/jn.00229.2001","article-title":"Coherent electrical activity between vibrissa sens.","volume":"87","author":"O\u2019Connor","year":"2002","journal-title":"J. Neurophysiol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"2989","DOI":"10.1098\/rstb.2011.0167","article-title":"Active touch sensing.","volume":"366","author":"Prescott","year":"2011","journal-title":"Philos. Trans. R. Soc. Lond B Biol. Sci."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1038\/nn.3773","article-title":"Cerebellum involvement in cortical sensorimotor circuits for the control of voluntary movements.","volume":"17","author":"Proville","year":"2014","journal-title":"Nat. Neurosci."},{"key":"B42","doi-asserted-by":"publisher","first-page":"e38852","DOI":"10.7554\/eLife.38852","article-title":"Potentiation of cerebellar Purkinje cells facilitates whisker reflex adaptation through increased simple spike activity.","volume":"7","author":"Romano","year":"2018","journal-title":"eLife"},{"key":"B43","doi-asserted-by":"publisher","first-page":"107867","DOI":"10.1016\/j.celrep.2020.107867","article-title":"Functional convergence of autonomic and sensorimotor processing in the lateral cerebellum.","volume":"32","author":"Romano","year":"2020","journal-title":"Cell Rep."},{"key":"B44","doi-asserted-by":"publisher","first-page":"8812","DOI":"10.1038\/s41467-025-64592-8","article-title":"Stage-dependent cerebrocerebellar communication during sensorimotor processing.","volume":"16","author":"Romano","year":"2025","journal-title":"Nat. Commun."},{"key":"B45","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1016\/j.cub.2021.12.020","article-title":"Olivocerebellar control of movement symmetry.","volume":"32","author":"Romano","year":"2022","journal-title":"Curr. Biol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"9537","DOI":"10.1523\/JNEUROSCI.0712-14.2014","article-title":"Natural whisker-guided behavior by head-fixed mice in tactile virtual reality.","volume":"34","author":"Sofroniew","year":"2014","journal-title":"J. Neurosci."},{"key":"B47","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1111\/ejn.12800","article-title":"Parallel pathways from motor and somatosensory cortex for controlling whisker movements in mice.","volume":"41","author":"Sreenivasan","year":"2015","journal-title":"Eur. J. Neurosci."},{"key":"B48","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1016\/j.neuron.2012.11.010","article-title":"New modules are added to vibrissal premotor circuitry with the emergence of exploratory whisking.","volume":"77","author":"Takatoh","year":"2013","journal-title":"Neuron"},{"key":"B49","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1038\/s41586-022-05144-8","article-title":"The whisking oscillator circuit.","volume":"609","author":"Takatoh","year":"2022","journal-title":"Nature"},{"key":"B50","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.neulet.2018.04.035","article-title":"Conditioned climbing fiber responses in cerebellar cortex and nuclei.","volume":"688","author":"Ten Brinke","year":"2019","journal-title":"Neurosci. Lett."},{"key":"B51","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/S0079-6123(00)24014-4","article-title":"Topography of cerebellar nuclear projections to the brain stem in the rat.","volume":"124","author":"Teune","year":"2000","journal-title":"Prog. Brain Res."},{"key":"B52","doi-asserted-by":"publisher","first-page":"8838","DOI":"10.1523\/JNEUROSCI.0581-06.2006","article-title":"Right-left asymmetries in the whisking behavior of rats anticipate head movements.","volume":"26","author":"Towal","year":"2006","journal-title":"J. Neurosci."},{"key":"B53","doi-asserted-by":"publisher","first-page":"e22400","DOI":"10.1371\/journal.pone.0022400","article-title":"Optogenetic manipulation of cerebellar Purkinje cell activity in vivo.","volume":"6","author":"Tsubota","year":"2011","journal-title":"PLoS One"},{"key":"B54","doi-asserted-by":"publisher","first-page":"3441","DOI":"10.1113\/jphysiol.2010.201582","article-title":"The mysterious microcircuitry of the cerebellar nuclei.","volume":"589","author":"Uusisaari","year":"2011","journal-title":"J. Physiol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1007\/s12311-010-0240-3","article-title":"Functional classification of neurons in the mouse lateral cerebellar nuclei.","volume":"10","author":"Uusisaari","year":"2011","journal-title":"Cerebellum"},{"key":"B56","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1152\/jn.00974.2006","article-title":"Morphological and electrophysiological properties of GABAergic and non-GABAergic cells in the deep cerebellar nuclei.","volume":"97","author":"Uusisaari","year":"2007","journal-title":"J. Neurophysiol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"6050","DOI":"10.1038\/s41467-020-19960-x","article-title":"A FN-MdV pathway and its role in cerebellar multimodular control of sensorimotor behavior.","volume":"11","author":"Wang","year":"2020","journal-title":"Nat. Commun."},{"key":"B58","doi-asserted-by":"publisher","first-page":"133","DOI":"10.3389\/fncir.2013.00133","article-title":"Strength and timing of motor responses mediated by rebound firing in the cerebellar nuclei after Purkinje cell activation.","volume":"7","author":"Witter","year":"2013","journal-title":"Front. Neural Circuits"},{"key":"B59","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1113\/JP284064","article-title":"Whisker kinematics in the cerebellum.","volume":"602","author":"Zhai","year":"2024","journal-title":"J. Physiol."}],"container-title":["Frontiers in Neural Circuits"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncir.2025.1706704\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T06:51:58Z","timestamp":1769064718000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncir.2025.1706704\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,22]]},"references-count":58,"alternative-id":["10.3389\/fncir.2025.1706704"],"URL":"https:\/\/doi.org\/10.3389\/fncir.2025.1706704","relation":{},"ISSN":["1662-5110"],"issn-type":[{"value":"1662-5110","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,22]]},"article-number":"1706704"}}