Quadrupedal locomotion arises from a complex interplay between spinal neuronal circuits, descending brain signals, musculoskeletal interactions, and sensory feedback, enabling adaptive speed and terrain-dependent gait transitions. However, the underlying neural mechanisms involved in limb coordination are poorly understood. Here, we present a proof-of-concept 3D closed-loop neuromechanical model of a mouse that can be used to study interactions between the spinal circuitry and afferent feedback and their role in limb coordination during quadrupedal locomotion. The spinal circuit model includes four rhythm generators, each controlling one limb, that define the locomotor frequency and flexor–extensor alternation. The rhythm generators control pattern formation circuits that generate muscle synergies and create muscle-specific activation patterns. Commissural and long propriospinal interneurons mediate (fore-hind and leftright) interlimb coordination. Afferent feedback (muscle spindle Ia and II, Golgi tendon Ib, and cutaneous) signals interact with the rhythm generators (affecting the timing of phase-transitions), the pattern formation circuits (affecting muscle synergies), and directly with the motoneurons and premotor interneurons, forming basic reflex circuits. Motoneurons activate the muscles to generate locomotor behaviors. Using evolutionary strategies, the model was successfully optimized to locomote over flat ground at different speeds. Acute removal of feedback caused the model to fall and illustrates the capabilities of the model to study neural manipulations. We envision this neuromechanical mouse model to serve as an open testbed to study neural mechanisms for control of complex locomotor behavior in 3D environment.

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