A brainstem monosynaptic excitatory pathway that drives locomotor activities and sympathetic cardiovascular responses

Satoshi Koba (), Nao Kumada, Emi Narai, Naoya Kataoka, Kazuhiro Nakamura and Tatsuo Watanabe
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Satoshi Koba: Tottori University Faculty of Medicine
Nao Kumada: Tottori University Faculty of Medicine
Emi Narai: Tottori University Faculty of Medicine
Naoya Kataoka: Nagoya University Graduate School of Medicine
Kazuhiro Nakamura: Nagoya University Graduate School of Medicine
Tatsuo Watanabe: Tottori University Faculty of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract Exercise including locomotion requires appropriate autonomic cardiovascular adjustments to meet the metabolic demands of contracting muscles, yet the functional brain architecture underlying these adjustments remains unknown. Here, we demonstrate brainstem circuitry that plays an essential role in relaying volitional motor signals, i.e., central command, to drive locomotor activities and sympathetic cardiovascular responses. Mesencephalic locomotor neurons in rats transmit central command-driven excitatory signals onto the rostral ventrolateral medulla at least partially via glutamatergic processes, to activate both somatomotor and sympathetic nervous systems. Optogenetic excitation of this monosynaptic pathway elicits locomotor and cardiovascular responses as seen during running exercise, whereas pathway inhibition suppresses the locomotor activities and blood pressure elevation during voluntary running without affecting basal cardiovascular homeostasis. These results demonstrate an important subcortical pathway that transmits central command signals, providing a key insight into the central circuit mechanism required for the physiological conditioning essential to maximize exercise performance.

Date: 2022
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DOI: 10.1038/s41467-022-32823-x

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