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V1 and V2b Interneurons Secure the Alternating Flexor-Extensor Motor Activity Mice Require for Limbed Locomotion
Open accessAbstract
Reciprocal activation of flexor and extensor muscles constitutes the fundamental mechanism that tetrapod vertebrates use for locomotion and limb-driven reflex behaviors. This aspect of motor coordination is controlled by inhibitory neurons in the spinal cord; however, the identity of the spinal interneurons that serve this function is not known. Here, we show that the production of an alternating flexor-extensor motor rhythm depends on the composite activities of two classes of ventrally located inhibitory neurons, V1 and V2b interneurons (INs). Abrogating V1 and V2b IN-derived neurotransmission in the isolated spinal cord results in a synchronous pattern of L2 flexor-related and L5 extensor-related locomotor activity. Mice lacking V1 and V2b inhibition are unable to articulate their limb joints and display marked deficits in limb-driven reflex movements. Taken together, these findings identify V1- and V2b-derived neurons as the core interneuronal components of the limb central pattern generator (CPG) that coordinate flexor-extensor motor activity.
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“For example, ventral inhibitory neurons (V1 and V2b neurons49,50), which are located downstream to SCVsx2::Hoxa10 neurons, were prioritized in specific comparisons involving the long-term recovery of walking following EESREHAB.”
From The neurons that restore walking after paralysis (2022) · cites this paper as [49]
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“…roles in regulating leftright coordination, rhythmogenesis and the speed of the step cycle, the cells that are responsible for establishing an alternating flexor-extensor rhythm have still not been isolated (Goulding, 2009; Grillner and Jessell, 2009; Kiehn, 2006; Stepien and Arber, 2008).”
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Decoding the organization of spinal circuits that control locomotion
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The neurons that restore walking after paralysis
Kathe, C., Skinnider, M. A., Hutson, T. H., Regazzi, N., Gautier, M., Demesmaeker, R., Komi, S., Ceto, S., James, N. D., Cho, N., et al. (2022) · Nature · doi:10.1038/s41586-022-05385-7 · Cited by 304
Metadata
- Authors
- Zhang, J., Lanuza, G. M., Britz, O., Wang, Z., Siembab, V. C., Zhang, Y., Velasquez, T., Alvarez, F. J., Frank, E., & Goulding, M.
- Affiliations
- Salk Institute for Biological Studies (US)
- Tufts University (US)
- Wright State University (US)
- Corresponding author
- Goulding, Martyn
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2014-04
- Volume
- 82
- Issue
- 1
- Pages
- 138-150
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC4096991
- OpenAlex
- W2080030366
- Cited by
- 233
- References
- 67
- Citations by year
- 2026: 11 · 2025: 22 · 2024: 21 · 2023: 22 · 2022: 21 · 2021: 18 · 2020: 15 · 2019: 17 · 2018: 24 · 2017: 18 · 2016: 18 · 2015: 20 · 2014: 6
- FWCI
- 9.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Journal of Bioresource Management (submittedVersion, cc-by)
- CONICET Digital (CONICET) (submittedVersion, cc-by-nc-sa)
- Funders
- National Institutes of Health
- Simons Institute for the Theory of Computing, University of California Berkeley
- National Institute of Neurological Disorders and Stroke (P01NS031249, R37NS037075, P01NS057228, R56NS047357, R01NS080586, R01NS047357)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Motor Control and Adaptation
- Physical Sciences › Engineering › Control and Systems Engineering › Robotic Locomotion and Control
- Keywords
- spinal interneurons, inhibitory neurotransmission, tetrapod locomotion
- MeSH terms
- Action Potentials, Animals, Animals, Newborn, Cholera Toxin, Embryo, Mammalian, Extremities, Interneurons, Functional Laterality, Locomotion, Mice, Transgenic, Motor Activity, Mutation, Neural Inhibition, Reflex, Spinal Cord, Tail, Neurotransmitter Agents, Muscle, Skeletal, Mice
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