Sensory convergence and inhibitory divergence: deep dorsal horn inhibitory interneurons modulate the timing and magnitude of limb coordination during locomotion

• Published in: bioRxiv
• Main Authors: Ozeri-Engelhard, Nofar, Gradwell, Mark A, Laflamme, Olivier D, Upadhyay, Aman, Aoki, Adin, Shrier, Tara, Gandhi, Melissa, Gonzalez, Melissa, Eisdorfer, Jaclyn T, Abbas- Zadeh, Gloria, Nusrath Yusuf, Zarghona Imtiaz, Alomary, Simona A, Katz, Jordan, Haas, Michael, Hernandez, Yurdiana, Akay, Turgay, Abraira, Victoria Eugenia
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 20.09.2022
• Subjects: Coordination; Dorsal horn; Interneurons; Kinematics; Locomotion; Motor task performance; Parvalbumin; Proprioception; Spinal cord
• DOI: 10.1101/2022.05.21.492933

To achieve smooth motor performance in a rich and changing sensory environment, motor outputs must be constantly updated in response to sensory feedback. Although proprioception and cutaneous information are known to modulate motor output, it is unclear whether they work together in the spinal cord to shape complex motor actions such as locomotion. Here we identify the medial deep dorsal horn as a hot zone of convergent proprioceptive and cutaneous input for locomotion. Due to increased responsiveness to sensory input, inhibitory interneurons in the medial deep dorsal horn area are preferentially recruited in locomotion. To study inhibitory interneurons in this area, we utilize an intersectional genetic strategy to isolate and ablate a population of parvalbumin-expressing glycinergic interneurons in the medial deep dorsal horn (dPVs). Using histological and electrophysiological methods we find that dPVs integrate convergent proprioceptive and cutaneous input while targeting diffuse ventral horn motor networks. dPV ablation paired with behavioral testing and EMG recordings reveals a role for dPVs in the timing and magnitude of muscle recruitment, controlling step-cycle transition, kinematics, and limb coordination in a state and phase-dependent manner. Together, our results suggest that convergent sensory inputs work in concert to coordinate the activity of dPVs, and in-turn regulate motor output in a contextually relevant manner. Competing Interest Statement The authors have declared no competing interest. Footnotes * fixing author name