Computational modeling of spinal circuits controlling limb coordination and gaits in quadrupeds
Abstract
Interactions between cervical and lumbar spinal circuits are mediated by long propriospinal neurons (LPNs). Ablation of descending LPNs in mice disturbs left-right coordination at high speeds without affecting fore-hind alternation. We developed a computational model of spinal circuits consisting of four rhythm generators coupled by commissural interneurons (CINs), providing left-right interactions, and LPNs, mediating homolateral and diagonal interactions. The proposed CIN and diagonal LPN connections contribute to speed-dependent gait transition from walk, to trot, and then to gallop and bound; the homolateral LPN connections ensure fore-hind alternation in all gaits. The model reproduces speed-dependent gait expression in intact and genetically transformed mice and the disruption of hindlimb coordination following ablation of descending LPNs. Inputs to CINs and LPNs can affect interlimb coordination and change gait independent of speed. We suggest that these interneurons represent the main targets for supraspinal and sensory afferent signals adjusting gait.
Article and author information
Author details
Funding
National Institutes of Health (R01 NS081713)
- Ilya A Rybak
National Institutes of Health (R01 NS090919)
- Ilya A Rybak
National Institutes of Health (R01 NS095366)
- Natalia A Shevtsova
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Ronald L Calabrese, Emory University, United States
Version history
- Received: August 5, 2017
- Accepted: November 21, 2017
- Accepted Manuscript published: November 22, 2017 (version 1)
- Version of Record published: December 12, 2017 (version 2)
Copyright
© 2017, Danner et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Further reading
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- Neuroscience
A series of recent studies identified key structures in the mesencephalic locomotor region and the caudal brainstem of mice involved in the initiation and control of slow (exploratory) and fast (escape-type) locomotion and gait. However, the interactions of these brainstem centers with each other and with the spinal locomotor circuits are poorly understood. Previously we suggested that commissural and long propriospinal interneurons are the main targets for brainstem inputs adjusting gait (Danner et al., 2017). Here, by extending our previous model, we propose a connectome of the brainstem-spinal circuitry and suggest a mechanistic explanation of the operation of brainstem structures and their roles in controlling speed and gait. We suggest that brainstem control of locomotion is mediated by two pathways, one controlling locomotor speed via connections to rhythm generating circuits in the spinal cord and the other providing gait control by targeting commissural and long propriospinal interneurons.
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- Neuroscience
Most nervous systems combine both transmitter-mediated and direct cell-cell communication, known as 'chemical' and 'electrical' synapses, respectively. Chemical synapses can be identified by their multiple structural components. Electrical synapses are, on the other hand, generally defined by the presence of a 'gap junction' (a cluster of intercellular channels) between two neuronal processes. However, while gap junctions provide the communicating mechanism, it is unknown whether electrical transmission requires the contribution of additional cellular structures. We investigated this question at identifiable single synaptic contacts on the zebrafish Mauthner cells, at which gap junctions coexist with specializations for neurotransmitter release and where the contact unequivocally defines the anatomical limits of a synapse. Expansion microscopy of these single contacts revealed a detailed map of the incidence and spatial distribution of proteins pertaining to various synaptic structures. Multiple gap junctions of variable size were identified by the presence of their molecular components. Remarkably, most of the synaptic contact's surface was occupied by interleaving gap junctions and components of adherens junctions, suggesting a close functional association between these two structures. In contrast, glutamate receptors were confined to small peripheral portions of the contact, indicating that most of the synaptic area functions as an electrical synapse. Thus, our results revealed the overarching organization of an electrical synapse that operates with not one, but multiple gap junctions, in close association with structural and signaling molecules known to be components of adherens junctions. The relationship between these intercellular structures will aid in establishing the boundaries of electrical synapses found throughout animal connectomes and provide insight into the structural organization and functional diversity of electrical synapses.