Locomotor Speed Control Circuits in the Caudal Brainstem

Overview

Journal Nature

Specialty Science

Date 2017 Oct 24

PMID 29059682

Citations 126

Authors

Paolo Capelli

Chiara Pivetta

Maria Soledad Esposito

Silvia Arber

Affiliations

Soon will be listed here.

Abstract

Locomotion is a universal behaviour that provides animals with the ability to move between places. Classical experiments have used electrical microstimulation to identify brain regions that promote locomotion, but the identity of neurons that act as key intermediaries between higher motor planning centres and executive circuits in the spinal cord has remained controversial. Here we show that the mouse caudal brainstem encompasses functionally heterogeneous neuronal subpopulations that have differential effects on locomotion. These subpopulations are distinguishable by location, neurotransmitter identity and connectivity. Notably, glutamatergic neurons within the lateral paragigantocellular nucleus (LPGi), a small subregion in the caudal brainstem, are essential to support high-speed locomotion, and can positively tune locomotor speed through inputs from glutamatergic neurons of the upstream midbrain locomotor region. By contrast, glycinergic inhibitory neurons can induce different forms of behavioural arrest mapping onto distinct caudal brainstem regions. Anatomically, descending pathways of glutamatergic and glycinergic LPGi subpopulations communicate with distinct effector circuits in the spinal cord. Our results reveal that behaviourally opposing locomotor functions in the caudal brainstem were historically masked by the unexposed diversity of intermingled neuronal subpopulations. We demonstrate how specific brainstem neuron populations represent essential substrates to implement key parameters in the execution of motor programs.

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References

Fenno L, Mattis J, Ramakrishnan C, Hyun M, Lee S, He M . Targeting cells with single vectors using multiple-feature Boolean logic. Nat Methods. 2014; 11(7):763-72. PMC: 4085277. DOI: 10.1038/nmeth.2996. View

Grillner S . Biological pattern generation: the cellular and computational logic of networks in motion. Neuron. 2006; 52(5):751-66. DOI: 10.1016/j.neuron.2006.11.008. View

Foster E, Wildner H, Tudeau L, Haueter S, Ralvenius W, Jegen M . Targeted ablation, silencing, and activation establish glycinergic dorsal horn neurons as key components of a spinal gate for pain and itch. Neuron. 2015; 85(6):1289-304. PMC: 4372258. DOI: 10.1016/j.neuron.2015.02.028. View

Goulding M . Circuits controlling vertebrate locomotion: moving in a new direction. Nat Rev Neurosci. 2009; 10(7):507-18. PMC: 2847453. DOI: 10.1038/nrn2608. View

Wickersham I, Finke S, Conzelmann K, Callaway E . Retrograde neuronal tracing with a deletion-mutant rabies virus. Nat Methods. 2006; 4(1):47-9. PMC: 2755236. DOI: 10.1038/nmeth999. View

Lin J, Knutsen P, Muller A, Kleinfeld D, Tsien R . ReaChR: a red-shifted variant of channelrhodopsin enables deep transcranial optogenetic excitation. Nat Neurosci. 2013; 16(10):1499-508. PMC: 3793847. DOI: 10.1038/nn.3502. View

Mori S, Matsuyama K, Mori F, Nakajima K . Supraspinal sites that induce locomotion in the vertebrate central nervous system. Adv Neurol. 2001; 87:25-40. View

Taniguchi H, He M, Wu P, Kim S, Paik R, Sugino K . A resource of Cre driver lines for genetic targeting of GABAergic neurons in cerebral cortex. Neuron. 2011; 71(6):995-1013. PMC: 3779648. DOI: 10.1016/j.neuron.2011.07.026. View

Basaldella E, Takeoka A, Sigrist M, Arber S . Multisensory Signaling Shapes Vestibulo-Motor Circuit Specificity. Cell. 2015; 163(2):301-12. DOI: 10.1016/j.cell.2015.09.023. View

10.

Garcia-Rill E, Skinner R . The mesencephalic locomotor region. I. Activation of a medullary projection site. Brain Res. 1987; 411(1):1-12. DOI: 10.1016/0006-8993(87)90675-5. View

11.

Roseberry T, Lee A, Lalive A, Wilbrecht L, Bonci A, Kreitzer A . Cell-Type-Specific Control of Brainstem Locomotor Circuits by Basal Ganglia. Cell. 2016; 164(3):526-37. PMC: 4733247. DOI: 10.1016/j.cell.2015.12.037. View

12.

Noga B, Kettler J, Jordan L . Locomotion produced in mesencephalic cats by injections of putative transmitter substances and antagonists into the medial reticular formation and the pontomedullary locomotor strip. J Neurosci. 1988; 8(6):2074-86. PMC: 6569345. View

13.

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 (Vienna). 2015; 123(7):695-729. PMC: 4919383. DOI: 10.1007/s00702-015-1475-4. View

14.

Satoh D, Pudenz C, Arber S . Context-Dependent Gait Choice Elicited by EphA4 Mutation in Lbx1 Spinal Interneurons. Neuron. 2016; 89(5):1046-58. DOI: 10.1016/j.neuron.2016.01.033. View

15.

Mori S . Integration of posture and locomotion in acute decerebrate cats and in awake, freely moving cats. Prog Neurobiol. 1987; 28(2):161-95. DOI: 10.1016/0301-0082(87)90010-4. View

16.

Bouvier J, Caggiano V, Leiras R, Caldeira V, Bellardita C, Balueva K . Descending Command Neurons in the Brainstem that Halt Locomotion. Cell. 2015; 163(5):1191-1203. PMC: 4899047. DOI: 10.1016/j.cell.2015.10.074. View

17.

Fuhrmann F, Justus D, Sosulina L, Kaneko H, Beutel T, Friedrichs D . Locomotion, Theta Oscillations, and the Speed-Correlated Firing of Hippocampal Neurons Are Controlled by a Medial Septal Glutamatergic Circuit. Neuron. 2015; 86(5):1253-64. DOI: 10.1016/j.neuron.2015.05.001. View

18.

Liang H, Paxinos G, Watson C . Projections from the brain to the spinal cord in the mouse. Brain Struct Funct. 2010; 215(3-4):159-86. DOI: 10.1007/s00429-010-0281-x. View

19.

Lee A, Hoy J, Bonci A, Wilbrecht L, Stryker M, Niell C . Identification of a brainstem circuit regulating visual cortical state in parallel with locomotion. Neuron. 2014; 83(2):455-466. PMC: 4151326. DOI: 10.1016/j.neuron.2014.06.031. View

20.

Kiehn O . Decoding the organization of spinal circuits that control locomotion. Nat Rev Neurosci. 2016; 17(4):224-38. PMC: 4844028. DOI: 10.1038/nrn.2016.9. View