Optic nerve injury impairs intrinsic mechanisms underlying electrical activity in a resilient retinal ganglion cell

Retinal ganglion cells (RGCs) are the sole output neurons of the retina and convey visual information to the brain via their axons in the optic nerve. Following an injury to the optic nerve, RGCs axons degenerate and many cells die. For example, a surgical model of compressive axon injury, the optic nerve crush (ONC), kills ~80% of RGCs after two weeks. Surviving cells are biased towards certain 'resilient' types, including several types that originally produced sustained firing to light stimulation. RGC survival may depend on activity level, and there is a limited understanding of how or why activity changes following optic nerve injury. Here we quantified the electrophysiological properties of a highly resilient RGC type, the sustained ON-Alpha RGC, seven days post-ONC with extracellular and whole-cell patch clamp recording. Both light- and current-driven firing were reduced after ONC, but synaptic inputs were largely intact. Resting membrane potential and input resistance were relatively unchanged, while voltage-gated currents were impaired, including a reduction in voltage-gated sodium channel density in the axon initial segment and function. Hyperpolarization or chelation of intracellular calcium partially rescued firing rates. These data suggest that an injured resilient RGC reduces its activity by a combination of reduced voltage-gated channel expression and function and downregulation of intrinsic excitability via a Ca2+-dependent mechanism without substantial changes in synaptic input. Reduced excitability may be due to degradation of the axon but could also be energetically beneficial for injured RGCs, preserving cellular energy for survival and regeneration. ### Competing Interest Statement The authors have declared no competing interest.