Abstract
Whisking and sniffing are predominant aspects of exploratory behaviour in rodents. Yet the neural mechanisms that generate and coordinate these and other orofacial motor patterns remain largely uncharacterized. Here we use anatomical, behavioural, electrophysiological and pharmacological tools to show that whisking and sniffing are coordinated by respiratory centres in the ventral medulla. We delineate a distinct region in the ventral medulla that provides rhythmic input to the facial motor neurons that drive protraction of the vibrissae. Neuronal output from this region is reset at each inspiration by direct input from the pre-Bötzinger complex, such that high-frequency sniffing has a one-to-one relationship with whisking, whereas basal respiration is accompanied by intervening whisks that occur between breaths. We conjecture that the respiratory nuclei, which project to other premotor regions for oral and facial control, function as a master clock for behaviours that coordinate with breathing.
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References
Smith, J. C., Abdala, A. P. L., Rybak, I. A. & Paton, J. F. R. Structural and functional architecture of respiratory networks in the mammalian brainstem. Phil. Trans. R. Soc. B 364, 2577–2587 (2009)
Nakamura, Y. & Katakura, N. Generation of masticatory rhythm in the brainstem. Neurosci. Res. 23, 1–19 (1995)
Travers, J. B., Dinardo, L. A. & Karimnamazi, H. Motor and premotor mechanisms of licking. Neurosci. Biobehav. Rev. 21, 631–647 (1997)
Alheid, G. F. & McCrimmon, D. R. The chemical neuroanatomy of breathing. Respir. Physiol. Neurobiol. 164, 3–11 (2008)
Feldman, J. L., Del Negro, C. A. & Gray, P. A. Understanding the rhythm of breathing: so near, yet so far. Annu. Rev. Physiol. 75, 423–452 (2013)
Garcia, A. J., Zanella, S., Koch, H., Doi, A. & Ramirez, J. M. Networks within networks: the neuronal control of breathing. Prog. Brain Res. 188, 31–50 (2011)
Welker, W. I. Analysis of sniffing of the albino rat. Behaviour 22, 223–244 (1964)
Brecht, M. & Freiwald, W. A. The many facets of facial interactions in mammals. Curr. Opin. Neurobiol. 22, 259–266 (2011)
Vincent, S. B. The function of the vibrissae in the behavior of the white rat. Behavior Monographs 1, 7–81 (1912)
Smith, J. C., Ellenberger, H. H., Ballanyi, K., Richter, D. W. & Feldman, J. L. Pre-Botzinger complex: a brainstem region that may generate respiratory rhythm in mammals. Science 254, 726–729 (1991)
Tan, W. et al. Silencing preBötzinger complex somatostatin-expressing neurons induces persistent apnea in awake rat. Nature Neurosci. 11, 538–540 (2008)
Dobbins, E. G. & Feldman, J. L. Brainstem network controlling descending drive to phrenic motoneurons in rat. J. Comp. Neurol. 347, 64–86 (1994)
Bieger, D. & Hopkins, D. A. Viscerotopic representation of the upper alimentary tract in the medulla oblongata in the rat: the nucleus ambiguus. J. Comp. Neurol. 262, 546–562 (1987)
Semba, K. & Komisaruk, B. R. Neural substrates of two different rhythmical vibrissal movements in the rat. Neuroscience 12, 761–774 (1984)
Berg, R. W. & Kleinfeld, D. Rhythmic whisking by rat: retraction as well as protraction of the vibrissae is under active muscular control. J. Neurophysiol. 89, 104–117 (2003)
Gao, P., Bermejo, R. & Zeigler, H. P. Vibrissa deaffentation and rodent whisking patterns: behavioral evidence for a central pattern generator. J. Neurosci. 21, 5374–5380 (2001)
Huangfu, D., Koshiya, N. & Guyenet, P. G. Central respiratory modulation of facial motoneurons in rats. Neurosci. Lett. 151, 224–228 (1993)
Onimaru, H., Kumagawa, Y. & Homma, I. Respiration-related rhythmic activity in the rostral medulla of newborn rats. J. Neurophysiol. 96, 55–61 (2006)
Lawson, E. E., Richter, D. W., Czyzyk-Krzeska, M. F., Bischoff, A. & Rudesill, R. C. Respiratory neuronal activity during apnea and other breathing patterns induced by laryngeal stimulation. J. Appl. Ohysiology 70, 2742–2749 (1991)
Fukuda, Y. & Honda, Y. Differences in respiratory neural activities between vagal (superior laryngeal), hypoglossal, and phrenic nerves in the anesthetized rat. Jpn. J. Physiol. 32, 387–398 (1982)
Ermentrout, G. B. & Kleinfeld, D. Traveling electrical waves in cortex: insights from phase dynamics and speculation on a computational role. Neuron 29, 33–44 (2001)
Sherrey, J. H. & Megirian, D. State dependence of upper airway respiratory motoneurons: functions of the cricothyroid and nasolabial muscles of the unanesthetized rat. Electroencephalogr. Clin. Neurophysiol. 43, 218–228 (1977)
Haidarliu, S., Golomb, D., Kleinfeld, D. & Ahissar, E. Dorsorostral snout muscles in the rat subserve coordinated movement for whisking and sniffing. Anat. Rec. 295, 1181–1191 (2012)
Dörfl, J. The musculature of the mystacial vibrissae of the white mouse. J. Anat. 135, 147–154 (1982)
Hill, D. N., Bermejo, R., Zeigler, H. P. & Kleinfeld, D. Biomechanics of the vibrissa motor plant in rat: rhythmic whisking consists of triphasic neuromuscular activity. J. Neurosci. 28, 3438–3455 (2008)
Takatoh, J. et al. New modules are added to vibrissal premotor circuitry with the emergence of exploratory whisking. Neuron 77, 346–360 (2013)
Isokawa-Akesson, M. & Komisaruk, B. R. Difference in projections to the lateral and medial facial nucleus: anatomically separate pathways for rhythmical vibrissa movement in rats. Exp. Brain Res. 65, 385–398 (1987)
Furuta, T. et al. Inhibitory gating of vibrissal inputs in the brainstem. J. Neurosci. 28, 1789–1797 (2008)
Chatterton, J. E. et al. Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits. Nature 415, 793–798 (2002)
Pagliardini, S. et al. Active expiration induced by excitation of ventral medulla in adult anesthetized rats. J. Neurosci. 31, 2895–2905 (2011)
Klein, B. G. & Rhoades, R. The representation of whisker follicle intrinsic musculature in the facial motor nucleus of the rat. J. Comp. Neurol. 232, 55–69 (1985)
Gray, P. A. et al. Developmental origin of preBötzinger complex respiratory neurons. J. Neurosci. 30, 14883–14895 (2010)
Bouvier, J. et al. Hindbrain interneurons and axon guidance signaling critical for breathing. Nature Neurosci. 13, 1066–1074 (2010)
Welzl, H. & Bures, J. Lick-synchronized breathing in rats. Physiol. Behav. 18, 751–753 (1977)
Koizumi, H. et al. Functional imaging, spatial reconstruction, and biophysical analysis of a respiratory motor circuit isolated in vitro . J. Neurosci. 28, 2353–2365 (2008)
Ono, T., Ishiwata, Y., Inaba, N., Kuroda, T. & Nakamura, Y. Modulation of the inspiratory-related activity of hypoglossal premotor neurons during ingestion and rejection in the decerebrate cat. J. Neurophysiol. 80, 48–58 (1998)
Travers, J. B., DiNardo, L. A. & Karimnamazi, H. Medullary reticular formation activity during ingestion and rejection in the awake rat. Exp. Brain Res. 130, 78–92 (2000)
Chen, Z., Travers, S. P. & Travers, J. B. Muscimol infusions in the brain stem reticular formation reversibly block ingestion in the awake rat. Am. J. Physiol. Regul. Integr. Comp. Physiol. 280, R1085–R1094 (2001)
DePuy, S. D., Kanbar, R., Coates, M. B., Stornetta, R. L. & Guyenet, P. G. Control of breathing by raphe obscurus serotonergic neurons in mice. J. Neurosci. 31, 1981–1990 (2011)
Doi, A. & Ramirez, J. M. Neuromodulation and the orchestration of the respiratory rhythm. Respir. Physiol. Neurobiol. 164, 96–104 (2008)
Hattox, A., Li, Y. & Keller, A. Serotonin regulates rhythmic whisking. Neuron 39, 343–352 (2003)
VanderMaelen, C. P. & Aghajanian, G. K. Intracellular studies showing modulation of facial motoneurone excitability by serotonin. Nature 287, 346–347 (1980)
Harish, O. & Golomb, D. Control of the firing patterns of vibrissa motoneurons by modulatory and phasic synaptic inputs: a modeling study. J. Neurophysiol. 103, 2684–2699 (2010)
Saito, Y., Ezure, K., Tanaka, I. & Osawa, M. Activity of neurons in ventrolateral respiratory groups during swallowing in decerebrate rats. Brain Dev. 25, 338–345 (2003)
Kleinfeld, D., Sachdev, R. N. S., Merchant, L. M., Jarvis, M. R. & Ebner, F. F. Adaptive filtering of vibrissa input in motor cortex of rat. Neuron 34, 1021–1034 (2002)
Lewis, T. L. Jr, Mao, T. & Svoboda, K. Myosin-dependent targeting of transmembrane proteins to neuronal dendrites. Nature Neurosci. 12, 568–576 (2009)
Uchida, N. & Mainen, Z. F. Speed and accuracy of olfactory discrimination in the rat. Nature Neurosci. 6, 1224–1229 (2003)
Ganguly, K. & Kleinfeld, D. Goal-directed whisking behavior increases phase-locking between vibrissa movement and electrical activity in primary sensory cortex in rat. Proc. Natl Acad. Sci. USA 101, 12348–12353 (2004)
O'Connor, D. H. et al. Vibrissa-based object localization in head-fixed mice. J. Neurosci. 30, 1947–1967 (2010)
Shusterman, R., Smear, M. C., Koulakov, A. A. & Rinberg, D. Precise olfactory responses tile the sniff cycle. Nature Neurosci. 14, 1039–1044 (2011)
Knutsen, P. M., Derdikman, D. & Ahissar, E. Tracking whisker and head movements in unrestrained behaving rodents. J. Neurophysiol. 93, 2294–2301 (2005)
Hill, D. N., Curtis, J. C., Moore, J. D. & Kleinfeld, D. Primary motor cortex reports efferent control of vibrissa position on multiple time scales. Neuron 72, 344–356 (2011)
Deschênes, M., Timofeeva, E. & Lavallee, P. The relay of high frequency sensory signals in the whisker-to-barreloid pathway. J. Neurosci. 23, 6778–6787 (2003)
Paxinos, G., Watson, C., Pennisi, M. & Topple, A. Bregma, lambda and the interaural midpoint in stereotaxic surgery with rats of different sex, strain and weight. J. Neurosci. Methods 13, 139–143 (1985)
Ghosh, S. et al. Sensory maps in the olfactory cortex defined by long-range viral tracing of single neurons. Nature 472, 217–220 (2011)
Paxinos, G. & Watson, C. The Rat Brain in Stereotaxic Coordinates 6th edn (Academic Press, 2007)
Ito, T. & Oliver, D. L. Origins of glutamatergic terminals in the inferior colliculus identified by retrograde transport and expression of VGLUT1 and VGLUT2 genes. Front. Neuroanat. 4, 135 (2010)
Acknowledgements
We thank A. Kepecs and F. Wang for sharing unpublished work, and these colleagues as well as M. S. Fee, J. L. Feldman, H. J. Karten, P. M. Knutsen, D. W. Matthews and K. Svoboda for discussions. We also thank K. Svoboda for sponsorship of the mouse experiments, M. Agrochao and B. el Jundi for assistance with these experiments, T. Ito and D. L. Oliver for use of their GlyT2 probe, K. K. Baldwin for the gift of the Sindbis viral vector and K. Yang for assistance with behavioural training. We are grateful to the Canadian Institutes of Health Research (grant MT-5877), the Howard Hughes Medical Institute, the Japan Society for the Promotion of Science (KAKENHI grants 23135519 and 24500409), the National Institutes of Health (grants NS058668, NS066664 and NS047101) and the US–Israeli Binational Science Foundation (grant 2003222).
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M.D., D.K. and J.D.M. planned the experiments and wrote the manuscript. M.D., T.F. and J.D.M. carried out the rat experiments with assistance from M.D. for the histology and vibrissae tracking. D.H. carried out the mouse experiments with surgical assistance from M.C.S. Data analysis was carried out by J.D.M. with methodological contributions from D.K.
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Supplementary Figures
This file contains Supplementary Figures 1-14 (PDF 9118 kb)
Kainic acid-induced whisking in a lightly anesthetized rat
Coordinated rhythmic movement of the ipsilateral vibrissae occurs after iontophoresis of kainic acid into the left ventral medulla. The same rat is shown both 60 and 160 minutes after the injection. All vibrissae except numbers C1 to C3 are clipped, and the video is displayed at 0.25-times the original speed. (WMV 2074 kb)
Whisking after electrolytic lesion of the vIRt in a freely moving rat
A lesion in the left vIRt impairs movement of the ipsilateral vibrissae. Quantification of the whisking behavior and the extent of the lesion in this rat is shown in Figure 5a-c. All vibrissae except numbers C1 to C4 are clipped, and the video is displayed at 0.30-times the original speed. (WMV 942 kb)
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Moore, J., Deschênes, M., Furuta, T. et al. Hierarchy of orofacial rhythms revealed through whisking and breathing. Nature 497, 205–210 (2013). https://doi.org/10.1038/nature12076
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DOI: https://doi.org/10.1038/nature12076
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