Multimodal sensory control of motor performance by glycinergic interneurons of the mouse spinal cord deep dorsal horn

Mark A Gradwell; Nofar Ozeri-Engelhard; Jaclyn T Eisdorfer; Olivier D Laflamme; Melissa Gonzalez; Aman Upadhyay; Laura Medlock; Tara Shrier; Komal R Patel; Adin Aoki; Melissa Gandhi; Gloria Abbas-Zadeh; Olisemaka Oputa; Joshua K Thackray; Matthew Ricci; Arlene George; Nusrath Yusuf; Jessica Keating; Zarghona Imtiaz; Simona A Alomary; Manon Bohic; Michael Haas; Yurdiana Hernandez; Steven A Prescott; Turgay Akay; Victoria E Abraira

doi:10.1016/j.neuron.2024.01.027

Multimodal sensory control of motor performance by glycinergic interneurons of the mouse spinal cord deep dorsal horn

Neuron. 2024 Apr 17;112(8):1302-1327.e13. doi: 10.1016/j.neuron.2024.01.027. Epub 2024 Mar 6.

Authors

Mark A Gradwell¹, Nofar Ozeri-Engelhard², Jaclyn T Eisdorfer¹, Olivier D Laflamme³, Melissa Gonzalez⁴, Aman Upadhyay², Laura Medlock⁵, Tara Shrier¹, Komal R Patel¹, Adin Aoki¹, Melissa Gandhi¹, Gloria Abbas-Zadeh¹, Olisemaka Oputa¹, Joshua K Thackray⁶, Matthew Ricci⁷, Arlene George¹, Nusrath Yusuf², Jessica Keating¹, Zarghona Imtiaz¹, Simona A Alomary¹, Manon Bohic¹, Michael Haas¹, Yurdiana Hernandez⁸, Steven A Prescott⁹, Turgay Akay¹⁰, Victoria E Abraira¹¹

Affiliations

¹ Cell Biology and Neuroscience Department, Rutgers University, The State University of New Jersey, New Brunswick, NJ, USA; W.M. Keck Center for Collaborative Neuroscience, Rutgers University, The State University of New Jersey, New Brunswick, NJ, USA.
² Cell Biology and Neuroscience Department, Rutgers University, The State University of New Jersey, New Brunswick, NJ, USA; W.M. Keck Center for Collaborative Neuroscience, Rutgers University, The State University of New Jersey, New Brunswick, NJ, USA; Neuroscience PhD program, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ, USA.
³ Dalhousie PhD program, Dalhousie University, Halifax, NS, Canada; Department of Medical Neuroscience, Atlantic Mobility Action Project, Brain Repair Center, Dalhousie University, Halifax, NS, Canada.
⁴ Cell Biology and Neuroscience Department, Rutgers University, The State University of New Jersey, New Brunswick, NJ, USA; W.M. Keck Center for Collaborative Neuroscience, Rutgers University, The State University of New Jersey, New Brunswick, NJ, USA; Department of Biomedical Engineering, Rutgers University, The State University of New Jersey, New Brunswick, NJ, USA.
⁵ Neurosciences & Mental Health, The Hospital for Sick Children, Toronto, ON, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada.
⁶ Cell Biology and Neuroscience Department, Rutgers University, The State University of New Jersey, New Brunswick, NJ, USA; W.M. Keck Center for Collaborative Neuroscience, Rutgers University, The State University of New Jersey, New Brunswick, NJ, USA; Human Genetics Institute of New Jersey, Rutgers University, The State University of New Jersey, Piscataway, NJ, USA; Tourette International Collaborative Genetics Study (TIC Genetics).
⁷ School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel.
⁸ W.M. Keck Center for Collaborative Neuroscience, Rutgers University, The State University of New Jersey, New Brunswick, NJ, USA.
⁹ Neurosciences & Mental Health, The Hospital for Sick Children, Toronto, ON, Canada; Department of Physiology, University of Toronto, Toronto, ON, Canada.
¹⁰ Department of Medical Neuroscience, Atlantic Mobility Action Project, Brain Repair Center, Dalhousie University, Halifax, NS, Canada.
¹¹ Cell Biology and Neuroscience Department, Rutgers University, The State University of New Jersey, New Brunswick, NJ, USA; W.M. Keck Center for Collaborative Neuroscience, Rutgers University, The State University of New Jersey, New Brunswick, NJ, USA. Electronic address: victoria.abraira@rutgers.edu.

PMID: 38452762
DOI: 10.1016/j.neuron.2024.01.027

Abstract

Sensory feedback is integral for contextually appropriate motor output, yet the neural circuits responsible remain elusive. Here, we pinpoint the medial deep dorsal horn of the mouse spinal cord as a convergence point for proprioceptive and cutaneous input. Within this region, we identify a population of tonically active glycinergic inhibitory neurons expressing parvalbumin. Using anatomy and electrophysiology, we demonstrate that deep dorsal horn parvalbumin-expressing interneuron (dPV) activity is shaped by convergent proprioceptive, cutaneous, and descending input. Selectively targeting spinal dPVs, we reveal their widespread ipsilateral inhibition onto pre-motor and motor networks and demonstrate their role in gating sensory-evoked muscle activity using electromyography (EMG) recordings. dPV ablation altered limb kinematics and step-cycle timing during treadmill locomotion and reduced the transitions between sub-movements during spontaneous behavior. These findings reveal a circuit basis by which sensory convergence onto dorsal horn inhibitory neurons modulates motor output to facilitate smooth movement and context-appropriate transitions.

Keywords: dorsal horn; glycinergic interneurons; inhibition; movement; proprioception; sensorimotor circuits; spinal cord; touch.

MeSH terms

Animals
Interneurons / physiology
Locomotion
Mice
Parvalbumins*
Posterior Horn Cells / physiology
Spinal Cord
Spinal Cord Dorsal Horn*

Substances

Parvalbumins