Abstract
The brainstem locomotor system is believed to be organized serially from the mesencephalic locomotor region (MLR) to reticulospinal neurons, which in turn project to locomotor neurons in the spinal cord. We identified brainstem muscarinoceptive neurons in lampreys (Petromyzon marinus) that received parallel inputs from the MLR and projected back to reticulospinal cells to amplify and extend the duration of locomotor output. These cells responded to muscarine with extended periods of excitation, received direct muscarinic excitation from the MLR and projected glutamatergic excitation to reticulospinal neurons. Targeted blockade of muscarine receptors over these neurons profoundly reduced MLR-induced excitation of reticulospinal neurons and markedly slowed MLR-evoked locomotion. The presence of these neurons forces us to rethink the organization of supraspinal locomotor control, to include a sustained feedforward loop that boosts locomotor output.
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Acknowledgements
We thank D. Veilleux for assistance with experiments, C. Valiquette for his expertise in computer programming and F. Bernard for help with the figures. We also thank E. Hamid and M. Alpert for comments and critical discussion of this manuscript. This work was funded by a grant from the National Institute of Neurological Disorders and Stroke (R01 NS052699) to S.A. and Individual and Group grants from the Canadian Institutes of Health Research (grant numbers 15129 and 15176), the Natural Sciences and Engineering Research Council of Canada (grant number 217435-01) and the Groupe de recherche sur le système nerveux central from the Fonds de la Recherche en Santé du Québec (grant number 5249 to R.D.). L.J. received a Jasper fellowship from the Groupe de recherche sur le système nerveux central.
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R.S. performed experiments and analyses and drafted the paper. L.J. performed experiments on the semi-intact preparation, performed analyses and helped edit the paper. R.D. helped supervise the project and edited and wrote sections of the paper. S.A. supervised the project, performed experiments and analyses, and edited the manuscript.
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Smetana, R., Juvin, L., Dubuc, R. et al. A parallel cholinergic brainstem pathway for enhancing locomotor drive. Nat Neurosci 13, 731–738 (2010). https://doi.org/10.1038/nn.2548
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DOI: https://doi.org/10.1038/nn.2548
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