XXXX Receptor Phosphorylation and Synaptic Colocalization on Motor Neurons Drive Maladaptive Plasticity below Complete @entity1566 (1,2,3).

@entity1 @entity563 @entity35 @entity7336 @entity10237 @entity140 @entity460 @entity6784 @entity1566 @entity7335
Clinical @entity1566 ( @entity1566 ) is accompanied by comorbid peripheral injury in 47% of @entity1 . @entity1 and animal modeling data have shown that painful @entity6784 undermine long-term recovery of locomotion through unknown mechanisms. Peripheral nociceptive stimuli induce maladaptive synaptic plasticity in dorsal horn sensory systems through @entity140 receptor (AMPAR) phosphorylation and trafficking to synapses. Here we test whether ventral horn motor neurons in @entity35 demonstrate similar experience-dependent maladaptive plasticity below a complete @entity1566 in vivo. Quantitative biochemistry demonstrated that @entity10237 ( @entity10237 ) rapidly and selectively increases AMPAR subunit @entity7335 @entity563 831 phosphorylation and localization to synapses in the injured spinal cord, while reducing synaptic @entity7336 . These changes predict motor dysfunction in the absence of cell death signaling, suggesting an opportunity for therapeutic reversal. Automated confocal time-course analysis of lumbar ventral horn motor neurons confirmed a time-dependent increase in synaptic @entity7335 with concurrent decrease in synaptic @entity7336 . Optical fractionation of neuronal plasma membranes revealed @entity7336 removal from extrasynaptic sites on motor neurons early after @entity10237 followed by removal from synapses 2 h later. As @entity7336 -lacking AMPARs are canonical @entity460 -permeable AMPARs (CP-AMPARs), their stimulus- and time-dependent insertion provides a therapeutic target for limiting @entity460 -dependent dynamic maladaptive plasticity after @entity1566 . Confirming this, a selective CP-AMPAR antagonist protected against @entity10237 -induced maladaptive spinal plasticity, restoring adaptive motor responses on a sensorimotor spinal training task. These findings highlight the critical involvement of AMPARs in experience-dependent spinal cord plasticity after injury and provide a pharmacologically targetable synaptic mechanism by which early postinjury experience shapes motor plasticity.
