Dynamic changes of excitatory and inhibitory synapses in layer II/III of the primary motor cortex after peripheral nerve repair

Abstract

Peripheral nerve injury disrupts communication between the primary motor cortex (M1) and the target muscle, leading to alterations in synaptic plasticity within the lesion projection zone (LPZ). While nerve repair holds the potential to restore this pathway and further modulate synaptic plasticity within the LPZ, the underlying mechanisms remain incompletely understood. In this study, 42 adult male Sprague Dawley rats underwent immediate repair following unilateral median nerve transection and categorized the functional recovery of the affected limb into three phases: the injury phase, recovery phase, and rehabilitation phase, corresponding to stages of muscle non-reinnervation, gradual reinnervation, and completed reinnervation, respectively. Another 12 rats were used as the control group. Our findings revealed that during these phases, excitatory synaptic transmission in M1 layer II/III pyramidal neurons initially decreases, then increases, and ultimately returns to baseline levels. Conversely, inhibitory synaptic transmission initially increases, then decreases, and remains reduced even after full peripheral recovery, accompanied by upregulation of inhibitory synaptic receptors. These findings suggest that excitatory and inhibitory synaptic plasticity play opposing roles in the nerve repair process, with excitatory plasticity primarily involved in short-term responses and inhibitory plasticity contributing to both short-term and long-term modulation.