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
-
- 2,374
- views
-
- 327
- downloads
-
- 20
- 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
Studying infant minds with movies is a promising way to increase engagement relative to traditional tasks. However, the spatial specificity and functional significance of movie-evoked activity in infants remains unclear. Here, we investigated what movies can reveal about the organization of the infant visual system. We collected fMRI data from 15 awake infants and toddlers aged 5–23 months who attentively watched a movie. The activity evoked by the movie reflected the functional profile of visual areas. Namely, homotopic areas from the two hemispheres responded similarly to the movie, whereas distinct areas responded dissimilarly, especially across dorsal and ventral visual cortex. Moreover, visual maps that typically require time-intensive and complicated retinotopic mapping could be predicted, albeit imprecisely, from movie-evoked activity in both data-driven analyses (i.e. independent component analysis) at the individual level and by using functional alignment into a common low-dimensional embedding to generalize across participants. These results suggest that the infant visual system is already structured to process dynamic, naturalistic information and that fine-grained cortical organization can be discovered from movie data.
-
- Neuroscience
Mesolimbic dopamine encoding of non-contingent rewards and reward-predictive cues has been well established. Considerable debate remains over how mesolimbic dopamine responds to aversion and in the context of aversive conditioning. Inconsistencies may arise from the use of aversive stimuli that are transduced along different neural paths relative to reward or the conflation of responses to avoidance and aversion. Here, we made intraoral infusions of sucrose and measured how dopamine and behavioral responses varied to the changing valence of sucrose. Pairing intraoral sucrose with malaise via injection of lithium chloride (LiCl) caused the development of a conditioned taste aversion (CTA), which rendered the typically rewarding taste of sucrose aversive upon subsequent re-exposure. Following CTA formation, intraoral sucrose suppressed the activity of ventral tegmental area dopamine neurons (VTADA) and nucleus accumbens (NAc) dopamine release. This pattern of dopamine signaling after CTA is similar to intraoral infusions of innately aversive quinine and contrasts with responses to sucrose when it was novel or not paired with LiCl. Dopamine responses were negatively correlated with behavioral reactivity to intraoral sucrose and predicted home cage sucrose preference. Further, dopamine responses scaled with the strength of the CTA, which was increased by repeated LiCl pairings and weakened through extinction. Thus, the findings demonstrate differential dopamine encoding of the same taste stimulus according to its valence, which is aligned to distinct behavioral responses.
