Rebuilding Spinal Circuit Computation Through a Patient-Specific Interneuron Precision Model

Spinal interneurons constitute the computational core of spinal circuitry, integrating excitatory and inhibitory inputs to generate the rhythmic patterns that drive locomotor, postural, and autonomic control. Their developmental logic, molecular diversity, and adaptive plasticity make them central determinants of functional recovery after spinal cord injury. Yet most regenerative strategies continue to emphasize cellular replacement rather than the restoration of the computational integrity of spinal networks. In this review, we reframe spinal repair as the reconstitution of circuit computation. We synthesize current insights into how embryonic patterning programs defined by SHH, Wnt, and BMP gradients, refined by Notch and retinoic acid signaling, and consolidated by axon guidance cues, establish interneuron diversity, connectivity, and network symmetry that together encode the logic of motor coordination. Spinal cord injury disrupts this developmental logic, fragmenting excitatory and inhibitory balance and desynchronizing rhythmic modules, while residual circuits retain latent capacity for resynchronization through plasticity and neuromodulation. Building upon this developmental and computational continuum, we propose the Patient Specific Interneuron Precision Model (PIPM), a closed loop framework that links patient specific biological states including progenitor competence, morphogen sensitivity, and metabolic tone to circuit level computation and recovery potential. By bridging molecular, physiological, and clinical insights, the PIPM establishes a systems logic that unifies biological competence with circuit recovery, positioning interneuron computation as the conceptual foundation for precision spinal cord regeneration.