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Local brainstem circuits contribute to reticulospinal output in the mouse

View ORCID ProfileJeremy W. Chopek, Ying Zhang, View ORCID ProfileRobert M Brownstone
doi: https://doi.org/10.1101/2021.01.11.426243
Jeremy W. Chopek
1Department of Medical Neuroscience, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada, B3H 4R2
2Department of Neuromuscular Diseases, UCL Queen Square, Institute of Neurology, University College London, London, UK, WC1N 3BG
3Department of Physiology and Pathophysiology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada, R3E OJ9
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  • For correspondence: Jeremy.chopek@umanitoba.ca r.brownstone@ucl.ac.uk
Ying Zhang
1Department of Medical Neuroscience, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada, B3H 4R2
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Robert M Brownstone
2Department of Neuromuscular Diseases, UCL Queen Square, Institute of Neurology, University College London, London, UK, WC1N 3BG
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  • ORCID record for Robert M Brownstone
  • For correspondence: Jeremy.chopek@umanitoba.ca r.brownstone@ucl.ac.uk
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ABSTRACT

Glutamatergic reticulospinal neurons in the gigantocellular reticular nucleus (GRN) of the medullary reticular formation can function as command neurons, transmitting motor commands to spinal cord circuits. Recent advances in our understanding of this neuron-dense region have been facilitated by the discovery of expression of the transcriptional regulator, Chx10, in excitatory reticulospinal neurons. Here, we address the capacity of local circuitry in the GRN to contribute to reticulospinal output. We define two sub-populations of Chx10-expressing neurons in this region, based on distinct electrophysiological properties and somata size (small and large), and show that these correspond to local interneurons and reticulospinal neurons, respectively. Using focal release of caged-glutamate combined with patch clamp recordings, we demonstrated that Chx10 neurons form microcircuits in which the Chx10 interneurons project to and facilitate the firing of Chx10 reticulospinal neurons. We discuss the implications of these microcircuits in terms of movement selection.

SIGNIFICANCE STATEMENT Reticulospinal neurons in the medullary reticular formation play a key role in movement. The transcriptional regulator Chx10 defines a population of glutamatergic neurons in this region, a proportion of which have been shown to be involved in stopping, steering, and modulating locomotion. While it has been shown that these neurons integrate descending inputs, we asked whether local processing also ultimately contributes to reticulospinal outputs. Here, we define Chx10-expressing medullary reticular formation interneurons and reticulospinal neurons, and demonstrate how the former modulate the output of the latter. The results shed light on the internal organization and microcircuit formation of reticular formation neurons.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 12, 2021.
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Local brainstem circuits contribute to reticulospinal output in the mouse
Jeremy W. Chopek, Ying Zhang, Robert M Brownstone
bioRxiv 2021.01.11.426243; doi: https://doi.org/10.1101/2021.01.11.426243
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Local brainstem circuits contribute to reticulospinal output in the mouse
Jeremy W. Chopek, Ying Zhang, Robert M Brownstone
bioRxiv 2021.01.11.426243; doi: https://doi.org/10.1101/2021.01.11.426243

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