Spinal V2b neurons reveal a role for ipsilateral inhibition in speed control
- Washington University School of Medicine, United States
- National Institute for Basic Biology, Japan
Abstract
The spinal cord contains a diverse array of interneurons that govern motor output. Traditionally, models of spinal circuits have emphasized the role of inhibition in enforcing reciprocal alternation between left and right sides or flexors and extensors. However, recent work has shown that inhibition also increases coincident with excitation during contraction. Here, using larval zebrafish, we investigate the V2b (Gata3+) class of neurons, which contribute to flexor-extensor alternation but are otherwise poorly understood. Using newly generated transgenic lines we define two stable subclasses with distinct neurotransmitter and morphological properties. These V2b subclasses synapse directly onto motor neurons with differential targeting to speed-specific circuits. In vivo, optogenetic manipulation of V2b activity modulates locomotor frequency: suppressing V2b neurons elicits faster locomotion, whereas activating V2b neurons slows locomotion. We conclude that V2b neurons serve as a brake on axial motor circuits. Together, these results indicate a role for ipsilateral inhibition in speed control.
Data availability
Datasets have been deposited on Dryad, https://dx.doi.org/10.5061/dryad.1d78mt2
-
Data from: Spinal V2b neurons reveal a role for ipsilateral inhibition in speed controlDryad, doi:10.5061/dryad.1d78mt2.
Article and author information
Author details
Funding
National BioResource Project
- Shin-ichi Higashijima
National Institute on Deafness and Other Communication Disorders (R00 DC012536)
- Martha W Bagnall
National Institute on Deafness and Other Communication Disorders (R01 DC016413)
- Martha W Bagnall
National Institute of Neurological Disorders and Stroke (F32 NS103247)
- Rebecca A Callahan
Alfred P. Sloan Foundation
- Martha W Bagnall
Pew Charitable Trusts
- Martha W Bagnall
McKnight Endowment Fund for Neuroscience
- Martha W Bagnall
Children's Discovery Institute
- Martha W Bagnall
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This research adheres to recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health and received approval by the Washington University Institutional Animal Care and Use Committee (protocol 20170228).
Copyright
© 2019, Callahan 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.
Metrics
-
- 2,509
- views
-
- 379
- downloads
-
- 41
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Spinal V2b neurons reveal a role for ipsilateral inhibition in speed control
eLife 8:e47837.
https://doi.org/10.7554/eLife.47837
Further reading
-
- Genetics and Genomics
- Neuroscience
The mammalian suprachiasmatic nucleus (SCN), situated in the ventral hypothalamus, directs daily cellular and physiological rhythms across the body. The SCN clockwork is a self-sustaining transcriptional-translational feedback loop (TTFL) that in turn coordinates the expression of clock-controlled genes (CCGs) directing circadian programmes of SCN cellular activity. In the mouse, the transcription factor, ZFHX3 (zinc finger homeobox-3), is necessary for the development of the SCN and influences circadian behaviour in the adult. The molecular mechanisms by which ZFHX3 affects the SCN at transcriptomic and genomic levels are, however, poorly defined. Here, we used chromatin immunoprecipitation sequencing to map the genomic localization of ZFHX3-binding sites in SCN chromatin. To test for function, we then conducted comprehensive RNA sequencing at six distinct times-of-day to compare the SCN transcriptional profiles of control and ZFHX3-conditional null mutants. We show that the genome-wide occupancy of ZFHX3 occurs predominantly around gene transcription start sites, co-localizing with known histone modifications, and preferentially partnering with clock transcription factors (CLOCK, BMAL1) to regulate clock gene(s) transcription. Correspondingly, we show that the conditional loss of ZFHX3 in the adult has a dramatic effect on the SCN transcriptome, including changes in the levels of transcripts encoding elements of numerous neuropeptide neurotransmitter systems while attenuating the daily oscillation of the clock TF Bmal1. Furthermore, various TTFL genes and CCGs exhibited altered circadian expression profiles, consistent with an advanced in daily behavioural rhythms under 12 h light–12 h dark conditions. Together, these findings reveal the extensive genome-wide regulation mediated by ZFHX3 in the central clock that orchestrates daily timekeeping in mammals.
-
- Neuroscience
Untangling the functional organisation of a brain region crucial for memory and learning helps reveal how individual differences are linked to variations in recall ability, aging and dopamine receptor distribution.
