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

SUMMARY To achieve smooth motor performance in a changing sensory environment, motor outputs must be constantly updated in response to sensory feedback. Inhibitory interneurons in the spinal cord play an essential role in shaping motor activity by gating the transmission of sensory information and setting the pattern and rhythm of motor neurons. Here, we identify the medial deep dorsal horn of the spinal cord as a “hot zone” of convergent proprioceptive and cutaneous information from the hindlimb, where inhibitory neurons show increased responsiveness to sensory input and are preferentially recruited during locomotion in comparison to excitatory neurons. We identify a novel population of glycinergic inhibitory neurons within the deep dorsal horn that express parvalbumin (dPV) and receive convergent proprioceptive and cutaneous input from the paw. We show that dPVs possess intrinsic properties that support spontaneous discharge, even in the absence of synaptic input. However, a drug cocktail mimicking descending input (5-HT, dopamine, NMDA) amplifies dPV output, while cutaneous and proprioceptive inputs shape the temporal dynamics of dPV activity. These findings suggest dPV-mediated inhibition is modulated by behavioral state and can be fine-tuned by sensory input. Using intersectional genetic strategies, we selectively target spinal cord dPVs and demonstrate their capacity to provide divergent ipsilateral inhibition to both pre-motor and motor networks of the ventral horn, thereby controlling the timing and magnitude of cutaneous-evoked muscle activity. Manipulating the activity of dPVs during treadmill locomotion results in altered limb kinematics at the transition of stance to swing and altered step cycle timing at increased speeds. To investigate the effects of manipulating dPV activity on broader sets of motor behaviors, we used depth vision and machine learning to quantify and scale naturalistic behavior. We find that although sub-movements remain stable, the transitions between sub-movements are reduced, suggesting a role in movement switching. In sum, our study reveals a new model by which sensory convergence and inhibitory divergence produce a surprisingly flexible influence on motor networks to increase the diversity of mechanisms by which sensory input facilitates smooth movement and context-appropriate transitions. Highlights Inhibitory deep dorsal horn interneurons integrate convergent proprioceptive and cutaneous sensory inputs from the paw and are preferentially recruited during locomotion. Deep dorsal horn parvalbumin+ interneurons (dPVs) represent a population of glycinergic interneurons that can provide sustained inhibitory control. Sensory input engages dPVs to facilitate inhibition with high temporal precision and reduced variability. dPVs contribute to the ipsilateral inhibitory control of motor and premotor networks of the ventral horn, thereby gating the magnitude and timing of cutaneous-evoked flexor and extensor muscle activity. In vivo , dPVs modulate gait dynamics in a state- and phase-dependent manner, to ensure smooth movement transitions between step-cycle phases and naturalistic sub-movements.

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.