AFFERENT FEEDBACK ENABLES ROBUST SIT-TO-STAND TRANSITIONS IN RESPONSE TO V3 STIMULATION: A NEUROMECHANICAL MODELING STUDY

Optogenetic stimulation of lumbar V3 neurons in mice broadly activates hindlimb muscles, eliciting flexor and extensor co-activation, with a bias towards extensor activation. The mouse extends its hindlimbs and transitions smoothly from sitting to standing. Yet, how simple activation of a class of interneurons can induce a controlled transition to stable standing is unknown.
Here, we present a neuromechanical model of a mouse hindlimb including hip, knee, ankle, and metatarsal-phalange joints. Hill-type muscles represent several major flexors, extensors, and bifunctional muscle groups. Proprioceptive feedback signals were connected to a simplified neural network model, implementing low-level spinal reflex circuits. V3 interneurons were modeled to provide excitatory input to interneurons and motoneurons.
Our simulations demonstrated bistable limb dynamics induced by direct V3-driven extensor motoneuron activation, depending on the gradual increase and decrease of V3 neuron activity. As the limb extends, moment arms of knee extensor muscles improve; once sufficient muscle force is produced to overcome gravity a positive feedback loop is triggered: the resulting extension enhances muscle leverage, further increasing torque production and thus driving a rapid transition from flexion to full extension. Incorporating sensory feedback pathways, including Ia reciprocal inhibition, group II excitation, and Ib disynaptic excitation, alongside flexor-extensor coactivation, reduced the bistable range and enabled a smooth, stable control of limb extension in response to V3 stimulation.
These findings suggest that low-level reflex circuits contribute to stabilizing posture and controlling limb responses triggered by broad neural activation, offering insight into mechanisms by which V3 stimulation could induce standing.