Locomotor rhythm generation linked to the output of spinal Shox2 excitatory interneurons
Open accessAbstract
Locomotion is controlled by spinal networks that generate rhythm and coordinate left-right and flexor-extensor patterning. Defined populations of spinal interneurons have been linked to patterning circuits; however, neurons comprising the rhythm-generating kernel have remained elusive. Here, we identify an ipsilaterally projecting excitatory interneuron population, marked by the expression of Shox2 that overlaps partially with V2a interneurons. Optogenetic silencing or blocking synaptic output of Shox2 interneurons (INs) in transgenic mice perturbed rhythm without an effect on pattern generation, whereas ablation of the Shox2 IN subset coinciding with the V2a population was without effect. Most Shox2 INs are rhythmically active during locomotion and analysis of synaptic connectivity showed that Shox2 INs contact other Shox2 INs, commissural neurons, and motor neurons, with preference for flexor motor neurons. Our findings focus attention on a subset of Shox2 INs that appear to participate in the rhythm-generating kernel for spinal locomotion.
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The differential gene expression analysis recovered multiple TFs with well-established differential expression patterns, including Shox2 in V2a neurons, Foxp2 in V1 neurons, Lhx4 in MNs and V2a neurons, Neurog3 and Uncx in V3 neurons, and high levels of Nr2f2, Nfia, Foxp1 and Creb5 in MNs.
“This recovered multiple TFs, many with well-established differential gene expression patterns, for example: Shox2 in V2a neurons”
From Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord (2019) · cites this paper as Dougherty et al., 2013
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- Authors
- Dougherty, K. J., Zagoraiou, L., Satoh, D., Rozani, I., Doobar, S., Arber, S., Jessell, T. M., & Kiehn, O.
- Affiliations
- Karolinska Institutet (SE)
- Howard Hughes Medical Institute (US)
- University of Basel (CH)
- Biomedical Research Foundation of the Academy of Athens (GR)
- Corresponding author
- Zagoraiou, Laskaro
- Kiehn, Ole
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2013-11
- Volume
- 80
- Issue
- 4
- Pages
- 920-933
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2061314910
- Cited by
- 229
- References
- 45
- Citations by year
- 2026: 7 · 2025: 20 · 2024: 13 · 2023: 16 · 2022: 31 · 2021: 23 · 2020: 21 · 2019: 22 · 2018: 15 · 2017: 16 · 2016: 19 · 2015: 16 · 2014: 10
- FWCI
- 7.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Physical Sciences › Engineering › Biomedical Engineering › Robotic Locomotion and Control
- Keywords
- locomotor rhythm generation, spinal cord, SHOX2, excitatory interneurons, V2a interneurons, spinal locomotor network, left-right asymmetry, commissural neurons, motor neurons, synaptic connectivity, optogenetic silencing
- MeSH terms
- Dependovirus, Animals, Axons, Immunohistochemistry, Interneurons, Locomotion, Male, Motor Neurons, Neural Pathways, Serotonin, Spinal Cord, N-Methylaspartate, In Situ Hybridization, Homeodomain Proteins, Excitatory Amino Acid Agonists, Glutamic Acid, Gene Silencing, Vesicular Glutamate Transport Protein 2, Mice, Electrophysiological Phenomena, Optogenetics
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