Small sensory spinal lesions that affect hand function in monkeys greatly alter primary afferent and motor neuron connections in the cord

Abstract

Small sensory spinal injuries induce plasticity across the neuraxis, but little is understood about their effect on segmental connections or motor neuron (MN) function.Here, we begin to address this at two levels. First, we compared afferent input distributions from the skin and muscles of the digits with corresponding MN pools to determine their spatial relationship, in both the normal state and 4-6 months after a unilateral dorsal root/dorsal column lesion (DRL/DCL), affecting digits 1-3. Second, we looked at specific changes to MN inputs and membrane properties that likely impact functional recovery. Monkeys received a targeted unilateral DRL/DCL, and 4-6 months later, cholera toxin subunit B (CT-B) was injected bilaterally into either the distal pads of digits 1-3, or related intrinsic hand muscles, to label inputs to the cord, and corresponding MNs. In controls (unlesioned side), cutaneous and proprioceptive afferents from digits 1-3 showed different distribution patterns but similar rostrocaudal spread within the dorsal horn from C1 to T2. In contrast, MNs were distributed across just two segments (C7-8). Following the lesion, sensory inputs were significantly diminished across all 10 segments, though this did not alter MN distributions. Afferent and monoamine inputs, as well as KCC2 cotransporters, were also significantly altered on the cell membrane of CT-B labeled MNs postlesion. In contrast, inhibitory neurotransmission and perineuronal net integrity were not altered at this prechronic timepoint. Our findings indicate that even a small sensory injury can significantly impact sensory and motor spinal neurons and provide new insight into the complex process of recovery.