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
-
- 2,411
- views
-
- 338
- downloads
-
- 22
- 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
Cerebellar dysfunction leads to postural instability. Recent work in freely moving rodents has transformed investigations of cerebellar contributions to posture. However, the combined complexity of terrestrial locomotion and the rodent cerebellum motivate new approaches to perturb cerebellar function in simpler vertebrates. Here, we adapted a validated chemogenetic tool (TRPV1/capsaicin) to describe the role of Purkinje cells — the output neurons of the cerebellar cortex — as larval zebrafish swam freely in depth. We achieved both bidirectional control (activation and ablation) of Purkinje cells while performing quantitative high-throughput assessment of posture and locomotion. Activation modified postural control in the pitch (nose-up/nose-down) axis. Similarly, ablations disrupted pitch-axis posture and fin-body coordination responsible for climbs. Postural disruption was more widespread in older larvae, offering a window into emergent roles for the developing cerebellum in the control of posture. Finally, we found that activity in Purkinje cells could individually and collectively encode tilt direction, a key feature of postural control neurons. Our findings delineate an expected role for the cerebellum in postural control and vestibular sensation in larval zebrafish, establishing the validity of TRPV1/capsaicin-mediated perturbations in a simple, genetically tractable vertebrate. Moreover, by comparing the contributions of Purkinje cell ablations to posture in time, we uncover signatures of emerging cerebellar control of posture across early development. This work takes a major step towards understanding an ancestral role of the cerebellum in regulating postural maturation.
-
- Neuroscience
Human-specific cognitive abilities depend on information processing in the cerebral cortex, where the neurons are significantly larger and their processes longer and sparser compared to rodents. We found that, in synaptically connected layer 2/3 pyramidal cells (L2/3 PCs), the delay in signal propagation from soma to soma is similar in humans and rodents. To compensate for the longer processes of neurons, membrane potential changes in human axons and/or dendrites must propagate faster. Axonal and dendritic recordings show that the propagation speed of action potentials (APs) is similar in human and rat axons, but the forward propagation of excitatory postsynaptic potentials (EPSPs) and the backward propagation of APs are 26 and 47% faster in human dendrites, respectively. Experimentally-based detailed biophysical models have shown that the key factor responsible for the accelerated EPSP propagation in human cortical dendrites is the large conductance load imposed at the soma by the large basal dendritic tree. Additionally, larger dendritic diameters and differences in cable and ion channel properties in humans contribute to enhanced signal propagation. Our integrative experimental and modeling study provides new insights into the scaling rules that help maintain information processing speed albeit the large and sparse neurons in the human cortex.
