Excitatory and Inhibitory Descending Commissural Interneurons Differentially Integrate Supraspinal and Segmental Sensory Signals

• Type of Material: Article
• Authors: Andrea Giorgi, Emory University; Abishag Tluang Cer, Emory University; Shruthi Mohan, Emory University; Marie-Claude Perreault, Emory University
• Language: English
• Date: 2023-07-05
• Publisher: Society for Neuroscience
• Publication Version: Final Published Version
• Copyright Statement: © 2023 the authors
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): https://doi.org/10.1523/JNEUROSCI.2015-22.2023
• Title of Journal or Parent Work: The Journal of Neuroscience
• Volume: 43
• Issue: 27
• Start Page: 5014
• End Page: 5029
• Grant/Funding Information: This work was supported by Craig H. Neilsen Foundation Grant 313238, National Institutes of Health–National Institute of Neurological Disorders and Stroke Grant R01 NS085387, and National Science Foundation Division of Biological Infrastructure Grant 2015317. We thank Renee Shaw for help with cryostat sectioning, histology, immunohistochemistry, and animal care; Brandon K. LaPallo for the provision of two retrogradely labeled preparations; and the Emory University Integrated Cellular Imaging Core for the use of a confocal microscope.
• Keywords: motor coordination; calcium imaging; excitation-inhibition; neonatal mouse; reticulospinal; lumbar spinal interneurons
• Research Categories: Biology, Neuroscience

Abstract

The limited information about how descending inputs from the brain and sensory inputs from the periphery use spinal cord interneurons (INs) is a major barrier to understanding how these inputs may contribute to motor functions under normal and pathologic conditions. Commissural interneurons (CINs) are a heterogeneous population of spinal INs that has been implicated in crossed motor responses and bilateral motor coordination (ability to use the right and left side of the body in a coordinated manner) and, therefore, are likely involved in many types of movement (e.g., dynamic posture stabilization, jumping, kicking, walking). In this study, we incorporate mouse genetics, anatomy, electrophysiology, and single-cell calcium imaging to investigate how a subset of CINs, those with descending axons called dCINs, are recruited by descending reticulospinal and segmental sensory signals independently and in combination. We focus on two groups of dCINs set apart by their principal neurotransmitter (glutamate and GABA) and identified as VGluT2+ dCINs and GAD2+ dCINs. We show that VGluT2+ and GAD2+ dCINs are both extensively recruited by reticulospinal and sensory input alone but that VGluT2+ and GAD2+ dCINs integrate these inputs differently. Critically, we find that when recruitment depends on the combined action of reticulospinal and sensory inputs (subthreshold inputs), VGluT2+ dCINs, but not GAD2+ dCINs, are recruited. This difference in the integrative capacity of VGluT2+ and GAD2+ dCINs represents a circuit mechanism that the reticulospinal and segmental sensory systems may avail themselves of to regulate motor behaviors both normally and after injury.