Distal axotomy enhances retrograde presynaptic excitability onto injured pyramidal neurons via trans-synaptic signaling

摘要: Injury of descending motor tracts remodels cortical circuitry and leads to enhanced neuronal excitability, thus influencing recovery following injury. The neuron-specific contributions remain unclear due the complex cellular composition connectivity CNS. We developed a microfluidics-based in vitro model system examine intrinsic synaptic remodeling axon damage. found that distal axotomy cultured rat pyramidal neurons caused dendritic spine loss at synapses onto injured followed by persistent retrograde enhancement presynaptic excitability over days. These results mirrored hyper-activity directly corticospinal hindlimb cortex layer Vb spinal cord contusion. In axotomy-induced hyper-excitability coincided with elimination inhibitory terminals, including those formed spines. identified netrin-1 as downregulated exogenous applied 2 days after injury normalized density, fraction inputs neurons. findings demonstrate novel for studying response provide new insights mechanisms contribute remodeling.