{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T09:15:33Z","timestamp":1794474933462,"version":"4.9.1"},"reference-count":74,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T00:00:00Z","timestamp":1690416000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T00:00:00Z","timestamp":1690416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","award":["R276-2018-183"],"award-info":[{"award-number":["R276-2018-183"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","award":["R345-2020-1769"],"award-info":[{"award-number":["R345-2020-1769"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF15OC0014186"],"award-info":[{"award-number":["NNF15OC0014186"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"EC | Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["REP-SCI-693038"],"award-info":[{"award-number":["REP-SCI-693038"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006442","name":"University of Copenhagen | Det Sundhedsvidenskabelige Fakultet, K\u00f8benhavns Universitet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006442","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Neurosci"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Arrest of ongoing movements is an integral part of executing motor programs. Behavioral arrest may happen upon termination of a variety of goal-directed movements or as a global motor arrest either in the context of fear or in response to salient environmental cues. The neuronal circuits that bridge with the executive motor circuits to implement a global motor arrest are poorly understood. We report the discovery that the activation of glutamatergic Chx10-derived neurons in the pedunculopontine nucleus (PPN) in mice arrests all ongoing movements while simultaneously causing apnea and bradycardia. This global motor arrest has a pause-and-play pattern with an instantaneous interruption of movement followed by a short-latency continuation from where it was paused. Mice naturally perform arrest bouts with the same combination of motor and autonomic features. The Chx10-PPN-evoked arrest is different to ventrolateral periaqueductal gray-induced freezing. Our study defines a motor command that induces a global motor arrest, which may be recruited in response to salient environmental cues to allow for a preparatory or arousal state, and identifies a locomotor-opposing role for rostrally biased glutamatergic neurons in the PPN.<\/jats:p>","DOI":"10.1038\/s41593-023-01396-3","type":"journal-article","created":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T12:02:36Z","timestamp":1690459356000},"page":"1516-1528","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Pedunculopontine Chx10+ neurons control global motor arrest in mice"],"prefix":"10.1038","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3923-5299","authenticated-orcid":false,"given":"Haizea","family":"Go\u00f1i-Erro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4302-0207","authenticated-orcid":false,"given":"Raghavendra","family":"Selvan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittorio","family":"Caggiano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7232-2904","authenticated-orcid":false,"given":"Roberto","family":"Leiras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5954-469X","authenticated-orcid":false,"given":"Ole","family":"Kiehn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,7,27]]},"reference":[{"key":"1396_CR1","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1093\/cercor\/bhm044","volume":"18","author":"DM Eagle","year":"2008","unstructured":"Eagle, D. M. et al. Stop-signal reaction-time task performance: role of prefrontal cortex and subthalamic nucleus. Cereb. Cortex 18, 178\u2013188 (2008).","journal-title":"Cereb. Cortex"},{"key":"1396_CR2","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1152\/jn.00995.2010","volume":"106","author":"G Mirabella","year":"2011","unstructured":"Mirabella, G., Pani, P. & Ferraina, S. Neural correlates of cognitive control of reaching movements in the dorsal premotor cortex of rhesus monkeys. J. Neurophysiol. 106, 1454\u20131466 (2011).","journal-title":"J. Neurophysiol."},{"key":"1396_CR3","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1038\/nn.3456","volume":"16","author":"R Schmidt","year":"2013","unstructured":"Schmidt, R., Leventhal, D. K., Mallet, N., Chen, F. & Berke, J. D. Canceling actions involves a race between basal ganglia pathways. Nat. Neurosci. 16, 1118\u20131124 (2013).","journal-title":"Nat. Neurosci."},{"key":"1396_CR4","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1037\/a0035230","volume":"121","author":"GD Logan","year":"2014","unstructured":"Logan, G. D., Van Zandt, T., Verbruggen, F. & Wagenmakers, E.-J. On the ability to inhibit thought and action: general and special theories of an act of control. Psychol. Rev. 121, 66\u201395 (2014).","journal-title":"Psychol. Rev."},{"key":"1396_CR5","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.neuron.2016.12.013","volume":"93","author":"JR Wessel","year":"2017","unstructured":"Wessel, J. R. & Aron, A. R. On the globality of motor suppression: unexpected events and their influence on behavior and cognition. Neuron 93, 259\u2013280 (2017).","journal-title":"Neuron"},{"key":"1396_CR6","doi-asserted-by":"crossref","first-page":"20160197","DOI":"10.1098\/rstb.2016.0197","volume":"372","author":"T Roseberry","year":"2017","unstructured":"Roseberry, T. & Kreitzer, A. Neural circuitry for behavioural arrest. Philos. Trans. R. Soc. Lond. Ser. B 372, 20160197\u201320160197 (2017).","journal-title":"Philos. Trans. R. Soc. Lond. Ser. B"},{"key":"1396_CR7","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1016\/j.cell.2015.10.074","volume":"163","author":"J Bouvier","year":"2015","unstructured":"Bouvier, J. et al. Descending command neurons in the brainstem that halt locomotion. Cell 163, 1191\u20131203 (2015).","journal-title":"Cell"},{"key":"1396_CR8","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1016\/j.celrep.2016.05.029","volume":"15","author":"L Juvin","year":"2016","unstructured":"Juvin, L. et al. A specific population of reticulospinal neurons controls the termination of locomotion. Cell Rep. 15, 2377\u20132386 (2016).","journal-title":"Cell Rep."},{"key":"1396_CR9","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1523\/JNEUROSCI.1992-18.2018","volume":"39","author":"S Gr\u00e4tsch","year":"2019","unstructured":"Gr\u00e4tsch, S. et al. A brainstem neural substrate for stopping locomotion. J. Neurosci. 39, 1044\u20131057 (2019).","journal-title":"J. Neurosci."},{"key":"1396_CR10","doi-asserted-by":"crossref","unstructured":"Botta, P. et al. An amygdala circuit mediates experience-dependent momentary arrests during exploration. Cell 183, 605\u2013619 (2020).","DOI":"10.1016\/j.cell.2020.09.023"},{"key":"1396_CR11","doi-asserted-by":"crossref","first-page":"429","DOI":"10.3758\/BF03210947","volume":"1","author":"MS Fanselow","year":"1994","unstructured":"Fanselow, M. S. Neural organization of the defensive behavior system responsible for fear. Psychon. Bull. Rev. 1, 429\u2013438 (1994).","journal-title":"Psychon. Bull. Rev."},{"key":"1396_CR12","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/nature17996","volume":"534","author":"P Tovote","year":"2016","unstructured":"Tovote, P. et al. Midbrain circuits for defensive behaviour. Nature 534, 206\u2013212 (2016).","journal-title":"Nature"},{"key":"1396_CR13","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.conb.2018.02.009","volume":"49","author":"JP Fadok","year":"2018","unstructured":"Fadok, J. P., Markovic, M., Tovote, P. & L\u00fcthi, A. New perspectives on central amygdala function. Curr. Opin. Neurobiol. 49, 141\u2013147 (2018).","journal-title":"Curr. Opin. Neurobiol."},{"key":"1396_CR14","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/S0306-4522(03)00095-2","volume":"119","author":"K Takakusaki","year":"2003","unstructured":"Takakusaki, K., Habaguchi, T., Ohtinata-Sugimoto, J., Saitoh, K. & Sakamoto, T. Basal ganglia efferents to the brainstem centers controlling postural muscle tone and locomotion: a new concept for understanding motor disorders in basal ganglia dysfunction. Neuroscience 119, 293\u2013308 (2003).","journal-title":"Neuroscience"},{"key":"1396_CR15","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1007\/s00702-015-1475-4","volume":"123","author":"K Takakusaki","year":"2016","unstructured":"Takakusaki, K., Chiba, R., Nozu, T. & Okumura, T. Brainstem control of locomotion and muscle tone with special reference to the role of the mesopontine tegmentum and medullary reticulospinal systems. J. Neural Transm. 123, 695\u2013729 (2016).","journal-title":"J. Neural Transm."},{"key":"1396_CR16","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1111\/j.1460-9568.2008.06576.x","volume":"29","author":"HL Wang","year":"2009","unstructured":"Wang, H. L. & Morales, M. Pedunculopontine and laterodorsal tegmental nuclei contain distinct populations of cholinergic, glutamatergic and GABAergic neurons in the rat. Eur. J. Neurosci. 29, 340\u2013358 (2009).","journal-title":"Eur. J. Neurosci."},{"key":"1396_CR17","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1002\/cne.22065","volume":"515","author":"J Mena-Segovia","year":"2009","unstructured":"Mena-Segovia, J., Micklem, B. R., Nair-Roberts, R. G., Ungless, M. A. & Bolam, J. P. GABAergic neuron distribution in the pedunculopontine nucleus defines functional subterritories. J. Comp. Neurol. 515, 397\u2013408 (2009).","journal-title":"J. Comp. Neurol."},{"key":"1396_CR18","doi-asserted-by":"crossref","first-page":"22","DOI":"10.3389\/fnana.2011.00022","volume":"5","author":"C Martinez-Gonzalez","year":"2011","unstructured":"Martinez-Gonzalez, C., Bolam, J. P. & Mena-Segovia, J. Topographical organization of the pedunculopontine nucleus. Front. Neuroanat. 5, 22 (2011).","journal-title":"Front. Neuroanat."},{"key":"1396_CR19","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1111\/j.1460-9568.2012.08002.x","volume":"35","author":"C Martinez-Gonzalez","year":"2012","unstructured":"Martinez-Gonzalez, C., Wang, H. L., Micklem, B. R., Bolam, J. P. & Mena-Segovia, J. Subpopulations of cholinergic, GABAergic and glutamatergic neurons in the pedunculopontine nucleus contain calcium-binding proteins and are heterogeneously distributed. Eur. J. Neurosci. 35, 723\u2013734 (2012).","journal-title":"Eur. J. Neurosci."},{"key":"1396_CR20","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.neuron.2017.02.027","volume":"94","author":"J Mena-Segovia","year":"2017","unstructured":"Mena-Segovia, J. & Bolam, J. P. Rethinking the pedunculopontine nucleus: from cellular organization to function. Neuron 94, 7\u201318 (2017).","journal-title":"Neuron"},{"key":"1396_CR21","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1002\/(SICI)1096-9861(19980808)395:3<359::AID-CNE7>3.0.CO;2-1","volume":"395","author":"I Grofova","year":"1998","unstructured":"Grofova, I. & Zhou, M. Nigral innervation of cholinergic and glutamatergic cells in the rat mesopontine tegmentum: light and electron microscopic anterograde tracing and immunohistochemical studies. J. Comp. Neurol. 395, 359\u2013379 (1998).","journal-title":"J. Comp. Neurol."},{"key":"1396_CR22","doi-asserted-by":"crossref","first-page":"S194","DOI":"10.1016\/j.parkreldis.2008.04.030","volume":"14","author":"P Winn","year":"2008","unstructured":"Winn, P. Experimental studies of pedunculopontine functions: are they motor, sensory or integrative? Parkinsonism Relat. Disord. 14, S194\u2013S198 (2008).","journal-title":"Parkinsonism Relat. Disord."},{"key":"1396_CR23","doi-asserted-by":"crossref","first-page":"4448","DOI":"10.2174\/1381612811319240011","volume":"19","author":"D Ryczko","year":"2013","unstructured":"Ryczko, D. & Dubuc, R. The multifunctional mesencephalic locomotor region. Curr. Pharm. Des. 19, 4448\u20134470 (2013).","journal-title":"Curr. Pharm. Des."},{"key":"1396_CR24","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1515\/tnsci-2015-0021","volume":"6","author":"E Garcia-Rill","year":"2015","unstructured":"Garcia-Rill, E., Luster, B., D\u2019Onofrio, S. & Mahaffey, S. Arousal, motor control, and parkinson\u2019s disease. Transl. Neurosci. 6, 198\u2013207 (2015).","journal-title":"Transl. Neurosci."},{"key":"1396_CR25","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1002\/mds.26556","volume":"31","author":"NK Gut","year":"2016","unstructured":"Gut, N. K. & Winn, P. The pedunculopontine tegmental nucleus\u2014a functional hypothesis from the comparative literature. Mov. Disord. 31, 615\u2013624 (2016).","journal-title":"Mov. Disord."},{"key":"1396_CR26","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.neuron.2014.06.031","volume":"83","author":"AM Lee","year":"2014","unstructured":"Lee, A. M. et al. Identification of a brainstem circuit regulating visual cortical state in parallel with locomotion. Neuron 83, 455\u2013466 (2014).","journal-title":"Neuron"},{"key":"1396_CR27","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.cell.2015.12.037","volume":"164","author":"TK Roseberry","year":"2016","unstructured":"Roseberry, T. K. et al. Cell-type-specific control of brainstem locomotor circuits by basal ganglia. Cell 164, 526\u2013537 (2016).","journal-title":"Cell"},{"key":"1396_CR28","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/nature25448","volume":"553","author":"V Caggiano","year":"2018","unstructured":"Caggiano, V. et al. Midbrain circuits that set locomotor speed and gait selection. Nature 553, 455\u2013460 (2018).","journal-title":"Nature"},{"key":"1396_CR29","doi-asserted-by":"crossref","first-page":"108123","DOI":"10.1016\/j.celrep.2020.108123","volume":"32","author":"MM Carvalho","year":"2020","unstructured":"Carvalho, M. M. et al. A brainstem locomotor circuit drives the activity of speed cells in the medial entorhinal cortex. Cell Rep. 32, 108123\u2013108123 (2020).","journal-title":"Cell Rep."},{"key":"1396_CR30","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/s41467-022-28075-4","volume":"13","author":"D Masini","year":"2022","unstructured":"Masini, D. & Kiehn, O. Targeted activation of midbrain neurons restores locomotor function in mouse models of parkinsonism. Nat. Commun. 13, 504 (2022).","journal-title":"Nat. Commun."},{"key":"1396_CR31","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/j.cub.2018.02.007","volume":"28","author":"N Josset","year":"2018","unstructured":"Josset, N. et al. Distinct contributions of mesencephalic locomotor region nuclei to locomotor control in the freely behaving mouse. Curr. Biol. 28, 884\u2013901 (2018).","journal-title":"Curr. Biol."},{"key":"1396_CR32","doi-asserted-by":"crossref","first-page":"109594","DOI":"10.1016\/j.celrep.2021.109594","volume":"36","author":"D Dautan","year":"2021","unstructured":"Dautan, D. et al. Modulation of motor behavior by the mesencephalic locomotor region. Cell Rep. 36, 109594\u2013109594 (2021).","journal-title":"Cell Rep."},{"key":"1396_CR33","unstructured":"Franklin, K. & Paxinos, G. The Mouse Brain in Stereotaxic Coordinates (Elsevier, 2007)."},{"key":"1396_CR34","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/nrn.2016.9","volume":"17","author":"O Kiehn","year":"2016","unstructured":"Kiehn, O. Decoding the organization of spinal circuits that control locomotion. Nat. Rev. Neurosci. 17, 224\u2013238 (2016).","journal-title":"Nat. Rev. Neurosci."},{"key":"1396_CR35","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/s41593-020-0633-7","volume":"23","author":"JM Cregg","year":"2020","unstructured":"Cregg, J. M. et al. Brainstem neurons that command mammalian locomotor asymmetries. Nat. Neurosci. 23, 730\u2013740 (2020).","journal-title":"Nat. Neurosci."},{"key":"1396_CR36","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nature13021","volume":"508","author":"E Azim","year":"2014","unstructured":"Azim, E., Jiang, J., Alstermark, B. & Jessell, T. M. Skilled reaching relies on a V2a propriospinal internal copy circuit. Nature 508, 357\u2013363 (2014).","journal-title":"Nature"},{"key":"1396_CR37","doi-asserted-by":"crossref","first-page":"14681","DOI":"10.1523\/JNEUROSCI.5231-12.2013","volume":"33","author":"F Bretzner","year":"2013","unstructured":"Bretzner, F. & Brownstone, R. M. Lhx3-Chx10 reticulospinal neurons in locomotor circuits. J. Neurosci. 33, 14681\u201314692 (2013).","journal-title":"J. Neurosci."},{"key":"1396_CR38","doi-asserted-by":"crossref","first-page":"2989","DOI":"10.1111\/j.1460-9568.2007.05906.x","volume":"26","author":"L Lundfald","year":"2007","unstructured":"Lundfald, L. et al. Phenotype of V2-derived interneurons and their relationship to the axon guidance molecule EphA4 in the developing mouse spinal cord. Eur. J. Neurosci. 26, 2989\u20133002 (2007).","journal-title":"Eur. J. Neurosci."},{"key":"1396_CR39","doi-asserted-by":"crossref","first-page":"3003","DOI":"10.1111\/j.1460-9568.2007.05907.x","volume":"26","author":"A Al-Mosawie","year":"2007","unstructured":"Al-Mosawie, A., Wilson, J. M. & Brownstone, R. M. Heterogeneity of V2-derived interneurons in the adult mouse spinal cord. Eur. J. Neurosci. 26, 3003\u20133015 (2007).","journal-title":"Eur. J. Neurosci."},{"key":"1396_CR40","doi-asserted-by":"crossref","first-page":"34","DOI":"10.3389\/fnana.2018.00034","volume":"12","author":"E Luquin","year":"2018","unstructured":"Luquin, E., Huerta, I., Aymerich, M. S. & Mengual, E. Stereological estimates of glutamatergic, GABAergic, and cholinergic neurons in the pedunculopontine and laterodorsal tegmental nuclei in the rat. Front. Neuroanat. 12, 34 (2018).","journal-title":"Front. Neuroanat."},{"key":"1396_CR41","doi-asserted-by":"crossref","unstructured":"Steinkellner, T., Yoo, J. H. & Hnasko, T. S. Differential expression of VGLUT2 in mouse mesopontine cholinergic neurons. eNeuro 6, ENEURO.0161-19.2019 (2019).","DOI":"10.1523\/ENEURO.0161-19.2019"},{"key":"1396_CR42","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.cell.2010.07.014","volume":"142","author":"DC Gray","year":"2010","unstructured":"Gray, D. C., Mahrus, S. & Wells, J. A. Activation of specific apoptotic caspases with an engineered small-molecule-activated protease. Cell 142, 637\u2013646 (2010).","journal-title":"Cell"},{"key":"1396_CR43","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.cell.2013.04.017","volume":"153","author":"CF Yang","year":"2013","unstructured":"Yang, C. F. et al. Sexually dimorphic neurons in the ventromedial hypothalamus govern mating in both sexes and aggression in males. Cell 153, 896\u2013909 (2013).","journal-title":"Cell"},{"key":"1396_CR44","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.resp.2003.08.002","volume":"138","author":"J Saponjic","year":"2003","unstructured":"Saponjic, J., Radulovacki, M. & Carley, D. W. Respiratory pattern modulation by the pedunculopontine tegmental nucleus. Respir. Physiol. Neurobiol. 138, 223\u2013237 (2003).","journal-title":"Respir. Physiol. Neurobiol."},{"key":"1396_CR45","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.resp.2010.06.006","volume":"173","author":"I Topchiy","year":"2010","unstructured":"Topchiy, I., Waxman, J., Radulovacki, M. & Carley, D. W. Functional topography of respiratory, cardiovascular and pontine-wave responses to glutamate microstimulation of the pedunculopontine tegmentum of the rat. Respir. Physiol. Neurobiol. 173, 64\u201370 (2010).","journal-title":"Respir. Physiol. Neurobiol."},{"key":"1396_CR46","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1126\/science.6849136","volume":"219","author":"DM Bramble","year":"1983","unstructured":"Bramble, D. M. & Carrier, D. R. Running and breathing in mammals. Science 219, 251\u2013256 (1983).","journal-title":"Science"},{"key":"1396_CR47","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/B978-0-444-53613-6.00012-5","volume":"187","author":"JF Gari\u00e9py","year":"2010","unstructured":"Gari\u00e9py, J. F., Missaghi, K. & Dubuc, R. The interactions between locomotion and respiration. Prog. Brain Res. 187, 173\u2013188 (2010).","journal-title":"Prog. Brain Res."},{"key":"1396_CR48","unstructured":"Leiras, R. et al. An excitatory midbrain motor circuit for evoking freezing behavior. Society for Neuroscience - SfN program no. 232.08 (2017)."},{"key":"1396_CR49","doi-asserted-by":"crossref","first-page":"54302","DOI":"10.7554\/eLife.54302","volume":"9","author":"CE Vaaga","year":"2020","unstructured":"Vaaga, C. E., Brown, S. T. & Raman, I. M. Cerebellar modulation of synaptic input to freezing-related neurons in the periaqueductal gray. eLife 9, 54302 (2020).","journal-title":"eLife"},{"key":"1396_CR50","doi-asserted-by":"crossref","unstructured":"Signoret-Genest, J. et al. Integrated cardio-behavioral responses to threat define defensive states. Nat. Neurosci. 26, 447\u2013457(2023).","DOI":"10.1038\/s41593-022-01252-w"},{"key":"1396_CR51","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0166-4328(93)90088-8","volume":"58","author":"P Carrive","year":"1993","unstructured":"Carrive, P. The periaqueductal gray and defensive behavior: functional representation and neuronal organization. Behav. Brain Res. 58, 27\u201347 (1993).","journal-title":"Behav. Brain Res."},{"key":"1396_CR52","doi-asserted-by":"crossref","first-page":"12274","DOI":"10.1523\/JNEUROSCI.4168-08.2008","volume":"28","author":"HH Subramanian","year":"2008","unstructured":"Subramanian, H. H., Balnave, R. J. & Holstege, G. The midbrain periaqueductal gray control of respiration. J. Neurosci. 28, 12274\u201312283 (2008).","journal-title":"J. Neurosci."},{"key":"1396_CR53","doi-asserted-by":"crossref","unstructured":"Brownstone, R. M. & Chopek, J. W. Reticulospinal systems for tuning motor commands. Front. Neural Circuits 12, 30 (2018).","DOI":"10.3389\/fncir.2018.00030"},{"key":"1396_CR54","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1007\/s00429-015-0993-z","volume":"221","author":"H Liang","year":"2016","unstructured":"Liang, H., Watson, C. & Paxinos, G. Terminations of reticulospinal fibers originating from the gigantocellular reticular formation in the mouse spinal cord. Brain Struct. Funct. 221, 1623\u20131633 (2016).","journal-title":"Brain Struct. Funct."},{"key":"1396_CR55","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/s41583-018-0003-6","volume":"19","author":"CA Del Negro","year":"2018","unstructured":"Del Negro, C. A., Funk, G. D. & Feldman, J. L. Breathing matters. Nat. Rev. Neurosci. 19, 351\u2013367 (2018).","journal-title":"Nat. Rev. Neurosci."},{"key":"1396_CR56","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1007\/PL00005755","volume":"116","author":"SD Stocker","year":"1997","unstructured":"Stocker, S. D., Steinbacher, B. C. Jr, Balaban, C. D. & Yates, B. J. Connections of the caudal ventrolateral medullary reticular formation in the cat brainstem. Exp. Brain Res. 116, 270\u2013282 (1997).","journal-title":"Exp. Brain Res."},{"key":"1396_CR57","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1002\/cne.20434","volume":"482","author":"W Sun","year":"2005","unstructured":"Sun, W. & Panneton, W. M. Defining projections from the caudal pressor area of the caudal ventrolateral medulla. J. Comp. Neurol. 482, 273\u2013293 (2005).","journal-title":"J. Comp. Neurol."},{"key":"1396_CR58","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/0166-2236(93)90090-9","volume":"16","author":"BL Jacobs","year":"1993","unstructured":"Jacobs, B. L. & Fornal, C. A. 5-HT and motor control: a hypothesis. Trends Neurosci. 16, 346\u2013352 (1993).","journal-title":"Trends Neurosci."},{"key":"1396_CR59","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/S0361-9230(00)00402-0","volume":"53","author":"BJ Schmidt","year":"2000","unstructured":"Schmidt, B. J. & Jordan, L. M. The role of serotonin in reflex modulation and locomotor rhythm production in the mammalian spinal cord. Brain Res. Bull. 53, 689\u2013710 (2000).","journal-title":"Brain Res. Bull."},{"key":"1396_CR60","doi-asserted-by":"crossref","first-page":"438","DOI":"10.2741\/1074","volume":"8","author":"BE Jones","year":"2003","unstructured":"Jones, B. E. Arousal systems. Front. Biosci. 8, 438\u2013451 (2003).","journal-title":"Front. Biosci."},{"key":"1396_CR61","doi-asserted-by":"crossref","first-page":"254","DOI":"10.2174\/157015908785777193","volume":"6","author":"E Samuels","year":"2008","unstructured":"Samuels, E. & Szabadi, E. Functional neuroanatomy of the noradrenergic locus coeruleus: its roles in the regulation of arousal and autonomic function part II: physiological and pharmacological manipulations and pathological alterations of locus coeruleus activity in humans. Curr. Neuropharmacol. 6, 254\u2013285 (2008).","journal-title":"Curr. Neuropharmacol."},{"key":"1396_CR62","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.neuron.2012.09.011","volume":"76","author":"SJ Sara","year":"2012","unstructured":"Sara, S. J. & Bouret, S. Orienting and reorienting: the locus coeruleus mediates cognition through arousal. Neuron 76, 130\u2013141 (2012).","journal-title":"Neuron"},{"key":"1396_CR63","doi-asserted-by":"crossref","first-page":"147226","DOI":"10.1016\/j.brainres.2020.147226","volume":"1755","author":"A Guillaumin","year":"2021","unstructured":"Guillaumin, A., Serra, G. P., Georges, F. & Wall\u00e9n-Mackenzie, \u00c5. Experimental investigation into the role of the subthalamic nucleus in motor control using optogenetics in mice. Brain Res. 1755, 147226\u2013147226 (2021).","journal-title":"Brain Res."},{"key":"1396_CR64","doi-asserted-by":"crossref","first-page":"7029","DOI":"10.1038\/s41380-021-01162-6","volume":"26","author":"L Parolari","year":"2021","unstructured":"Parolari, L., Schneeberger, M., Heintz, N. & Friedman, J. M. Functional analysis of distinct populations of subthalamic nucleus neurons on Parkinson\u2019s disease and OCD-like behaviors in mice. Mol. Psychiatry 26, 7029\u20137046 (2021).","journal-title":"Mol. Psychiatry"},{"key":"1396_CR65","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0306-4522(97)83047-3","volume":"78","author":"P Carrive","year":"1997","unstructured":"Carrive, P., Leung, P., Harris, J. & Paxinos, G. Conditioned fear to context is associated with increased Fos expression in the caudal ventrolateral region of the midbrain periaqueductal gray. Neuroscience 78, 165\u2013177 (1997).","journal-title":"Neuroscience"},{"key":"1396_CR66","doi-asserted-by":"crossref","unstructured":"Bradfield, L. A., Hart, G. & Balleine, B. W. The role of the anterior, mediodorsal, and parafascicular thalamus in instrumental conditioning. Front. Syst. Neurosci. 7, 51 (2013).","DOI":"10.3389\/fnsys.2013.00051"},{"key":"1396_CR67","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1007\/s00702-017-1713-z","volume":"125","author":"K Yamanaka","year":"2018","unstructured":"Yamanaka, K. et al. Roles of centromedian parafascicular nuclei of thalamus and cholinergic interneurons in the dorsal striatum in associative learning of environmental events. J. Neural Transm. 125, 501\u2013513 (2018).","journal-title":"J. Neural Transm."},{"key":"1396_CR68","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1097\/01.wnr.0000187629.38010.12","volume":"16","author":"P Mazzone","year":"2005","unstructured":"Mazzone, P. et al. Implantation of human pedunculopontine nucleus: a safe and clinically relevant target in Parkinson\u2019s disease. Neuroreport 16, 1877\u20131881 (2005).","journal-title":"Neuroreport"},{"key":"1396_CR69","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1093\/brain\/awl346","volume":"130","author":"A Stefani","year":"2007","unstructured":"Stefani, A. et al. Bilateral deep brain stimulation of the pedunculopontine and subthalamic nuclei in severe Parkinson\u2019s disease. Brain 130, 1596\u20131607 (2007).","journal-title":"Brain"},{"key":"1396_CR70","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1093\/brain\/awp229","volume":"133","author":"MU Ferraye","year":"2010","unstructured":"Ferraye, M. U. et al. Effects of pedunculopontine nucleus area stimulation on gait disorders in Parkinson\u2019s disease. Brain 133, 205\u2013214 (2010).","journal-title":"Brain"},{"key":"1396_CR71","doi-asserted-by":"crossref","first-page":"4792","DOI":"10.1523\/JNEUROSCI.3646-14.2015","volume":"35","author":"NK Gut","year":"2015","unstructured":"Gut, N. K. & Winn, P. Deep brain stimulation of different pedunculopontine targets in a novel rodent model of parkinsonism. J. Neurosci. 35, 4792\u20134803 (2015).","journal-title":"J. Neurosci."},{"key":"1396_CR72","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1002\/mds.27098","volume":"33","author":"W Thevathasan","year":"2018","unstructured":"Thevathasan, W. et al. Pedunculopontine nucleus deep brain stimulation in Parkinson\u2019s disease: a clinical review. Mov. Disord. 33, 10\u201320 (2018).","journal-title":"Mov. Disord."},{"key":"1396_CR73","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1038\/s41593-018-0209-y","volume":"21","author":"A Mathis","year":"2018","unstructured":"Mathis, A. et al. DeepLabCut: markerless pose estimation of user-defined body parts with deep learning. Nat. Neurosci. 21, 1281\u20131289 (2018).","journal-title":"Nat. Neurosci."},{"key":"1396_CR74","doi-asserted-by":"crossref","unstructured":"He, K., Zhang, X., Ren, S. & Sun, J. Deep residual learning for image recognition. In 2016 IEEE Conference on Computer Vision and Pattern Recognition 770\u2013778 (2016).","DOI":"10.1109\/CVPR.2016.90"}],"updated-by":[{"DOI":"10.1038\/s41593-023-01422-4","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T00:00:00Z","timestamp":1691712000000}}],"container-title":["Nature Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41593-023-01396-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41593-023-01396-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41593-023-01396-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T19:04:05Z","timestamp":1693508645000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41593-023-01396-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,27]]},"references-count":74,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2023,9]]}},"alternative-id":["1396"],"URL":"https:\/\/doi.org\/10.1038\/s41593-023-01396-3","relation":{},"ISSN":["1097-6256","1546-1726"],"issn-type":[{"value":"1097-6256","type":"print"},{"value":"1546-1726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,27]]},"assertion":[{"value":"21 April 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 June 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 July 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 August 2023","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s41593-023-01422-4","URL":"https:\/\/doi.org\/10.1038\/s41593-023-01422-4","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}