| Autor: |
Nofar Ozeri-Engelhard, Mark A Gradwell, Olivier D Laflamme, Aman Upadhyay, Adin Aoki, Tara Shrier, Melissa Gandhi, Melissa Gonzalez, Jaclyn T Eisdorfer, Gloria Abbas- Zadeh, Nusrath Yusuf, Zarghona Imtiaz, Simona A Alomary, Jordan Katz, Michael Haas, Yurdiana Hernandez, Turgay Akay, Victoria Abraira |
| Rok vydání: |
2022 |
| DOI: |
10.1101/2022.05.21.492933 |
| Popis: |
SUMMARYTo 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.HighlightsInhibitory interneurons in the medial deep dorsal horn (mDDH), functionally represented by a large glycinergic PV expressing subpopulation (dPVs), receive convergent input from cutaneous receptors and proprioceptors and are preferentially recruited during locomotion.While dPVs diffusely target motor networks, the temporal dynamics of their activity is regulated by incoming inputs, suggesting a role in modulation of motor output timing.Ablation of dPVs alters stance-to-swing transition and step frequency during high-speed locomotion, likely to result from loss of sensory mediated muscle inhibition.Ablation of dPVs alters joint kinematics at the transition from stance-to-swing, likely to result from loss of sensory mediated muscle amplitude attenuation. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
