Spinal premotor interneurons controlling antagonistic muscles are spatially intermingled
- University College London, United Kingdom
- Max Delbrück Center for Molecular Medicine, Germany
- Salk Institute for Biological Studies, United States
- University of Glasgow, United Kingdom
- Howard Hughes Medical Institute, Harvard University, United States
Abstract
Elaborate behaviours are produced by tightly controlled flexor-extensor motor neuron activation patterns. Motor neurons are regulated by a network of interneurons within the spinal cord, but the computational processes involved in motor control are not fully understood. The neuroanatomical arrangement of motor and premotor neurons into topographic patterns related to their controlled muscles is thought to facilitate how information is processed by spinal circuits. Rabies retrograde monosynaptic tracing has been used to label premotor interneurons innervating specific motor neuron pools, with previous studies reporting topographic mediolateral positional biases in flexor and extensor premotor interneurons. To more precisely define how premotor interneurons contacting specific motor pools are organized, we used multiple complementary viral-tracing approaches in mice to minimize systematic biases associated with each method. Contrary to expectations, we found that premotor interneurons contacting motor pools controlling flexion and extension of the ankle are highly intermingled rather than segregated into specific domains like motor neurons. Thus, premotor spinal neurons controlling different muscles process motor instructions in the absence of clear spatial patterns among the flexor-extensor circuit components.
Data availability
All data generated during this study are included in the manuscript and supporting files. We also provide a link to two GitHub repositories: one includes the whole manuscript in a MATLAB executable format (requires a licence) that allows the reader to interact with the original plots and change the settings of the gaussian kernel used to represent the data. The second is a GitHub repository containing the R version of the manuscript
Article and author information
Author details
Robert M Brownstone
Funding
Biotechnology and Biological Sciences Research Council (BB/L001454)
- Andrew J Todd
- David J Maxwell
- Marco Beato
Marguerite Vogt Award
- Bianca K Barriga
Brain Research UK
- Robert M Brownstone
Deutsche Forschungsgemeinschaft (ZA 885/1-1)
- Sophie Skarlatou
- Niccolò Zampieri
Deutsche Forschungsgemeinschaft (EXC 257 NeuroCure)
- Sophie Skarlatou
- Niccolò Zampieri
Benjamin Lewis Chair in Neuroscience
- Samuel L Pfaff
Sol Goldman Charitable Trust
- Samuel L Pfaff
National Institute of health (1 U19 NS112959-01)
- Samuel L Pfaff
National Institute of health (1 R01 NS123160-01)
- Samuel L Pfaff
Wellcome Trust (225674/Z/22/Z)
- Remi Ronzano
Biotechnology and Biological Sciences Research Council (BB/S005943/1)
- Marco Beato
Leverhulme Trust (RPG-2013-176)
- Marco Beato
Wellcome Trust (110193)
- Robert M Brownstone
Jane Coffin Childs Memorial Fund for Medical Research
- Jeffrey D Moore
Eunice Kennedy Shriver National Institute of Child Health and Human Development (5K99HD096512)
- Jeffrey D Moore
University of California, San Diego (T32 GM007240)
- Bianca K Barriga
Timken-Sturgis foundation
- Bianca K Barriga
Salk Institute for Biological Studies
- Bianca K Barriga
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experiments were performed in strict adherence to the Animals (Scientific Procedures) Act UK (1986) and certified by the UCL AWERB committee, under project licence number 70/9098. All experiments performed at the MDC were carried out in compliance with the German Animal Welfare Act and approved by the Regional Office for Health and Social Affairs Berlin (LAGeSo). All experiments performed at the Salk Institute were conducted in accordance with IACUC and AAALAC guidelines of the Salk Institute for Biological Studies. All surgeries were performed under general isofluorane anaesthesia. The mice were closely monitored for a 24-hr period following surgery to detect any sign of distress or motor impairment. Every effort was made to minimize suffering.
Copyright
© 2022, Ronzano 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
-
- 2,312
- views
-
- 318
- downloads
-
- 16
- 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 premotor interneurons controlling antagonistic muscles are spatially intermingled
eLife 11:e81976.
https://doi.org/10.7554/eLife.81976
Further reading
-
- Neuroscience
Biological memory networks are thought to store information by experience-dependent changes in the synaptic connectivity between assemblies of neurons. Recent models suggest that these assemblies contain both excitatory and inhibitory neurons (E/I assemblies), resulting in co-tuning and precise balance of excitation and inhibition. To understand computational consequences of E/I assemblies under biologically realistic constraints we built a spiking network model based on experimental data from telencephalic area Dp of adult zebrafish, a precisely balanced recurrent network homologous to piriform cortex. We found that E/I assemblies stabilized firing rate distributions compared to networks with excitatory assemblies and global inhibition. Unlike classical memory models, networks with E/I assemblies did not show discrete attractor dynamics. Rather, responses to learned inputs were locally constrained onto manifolds that ‘focused’ activity into neuronal subspaces. The covariance structure of these manifolds supported pattern classification when information was retrieved from selected neuronal subsets. Networks with E/I assemblies therefore transformed the geometry of neuronal coding space, resulting in continuous representations that reflected both relatedness of inputs and an individual’s experience. Such continuous representations enable fast pattern classification, can support continual learning, and may provide a basis for higher-order learning and cognitive computations.
-
- Neuroscience
Movie-watching is a central aspect of our lives and an important paradigm for understanding the brain mechanisms behind cognition as it occurs in daily life. Contemporary views of ongoing thought argue that the ability to make sense of events in the ‘here and now’ depend on the neural processing of incoming sensory information by auditory and visual cortex, which are kept in check by systems in association cortex. However, we currently lack an understanding of how patterns of ongoing thoughts map onto the different brain systems when we watch a film, partly because methods of sampling experience disrupt the dynamics of brain activity and the experience of movie-watching. Our study established a novel method for mapping thought patterns onto the brain activity that occurs at different moments of a film, which does not disrupt the time course of brain activity or the movie-watching experience. We found moments when experience sampling highlighted engagement with multi-sensory features of the film or highlighted thoughts with episodic features, regions of sensory cortex were more active and subsequent memory for events in the movie was better—on the other hand, periods of intrusive distraction emerged when activity in regions of association cortex within the frontoparietal system was reduced. These results highlight the critical role sensory systems play in the multi-modal experience of movie-watching and provide evidence for the role of association cortex in reducing distraction when we watch films.
