Language
English
Publication Date
11-1-2025
Journal
Journal of Physiology
DOI
10.1113/JP286414
PMID
39985791
PMCID
PMC12353978
PubMedCentral® Posted Date
2-22-2026
PubMedCentral® Full Text Version
Author MSS
Abstract
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 injury to the optic nerve, RGCs axons degenerate and many cells die. For example, a model of axon injury, the optic nerve crush (ONC), kills ~80% of RGCs after two weeks. Surviving cells are biased towards ‘resilient’ types, including several with sustained firing to light stimulation. RGC survival may depend on activity, and there is 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 (AlphaONS) 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 current and channel density in the axon initial segment. Hyperpolarization or chelation of intracellular calcium partially rescued firing rates. Extracellular recordings at three days post-ONC, showed normal light-evoked firing from AlphaONS RGCs and other Alpha RGCs, including susceptible types. These data suggest that an injured resilient RGC reduces its activity by one week post-injury as a consequence of reduced voltage-gated current and downregulation of intrinsic excitability via a Ca2+-dependent mechanism. Reduced excitability may be due to degradation of the axon but could also be energetically beneficial, preserving energy for survival and regeneration.
Keywords
Retinal Ganglion Cells, Animals, Optic Nerve Injuries, Male, Action Potentials, Axons, Mice, Calcium, Membrane Potentials, Voltage-Gated Sodium Channels, Mice, Inbred C57BL
Published Open-Access
yes
Recommended Citation
Thomas E Zapadka, Nicholas M Tran, and Jonathan B Demb, "Optic Nerve Injury Impairs Intrinsic Mechanisms Underlying Electrical Activity in a Resilient Retinal Ganglion Cell" (2025). Faculty, Staff and Students Publications. 7175.
https://digitalcommons.library.tmc.edu/baylor_docs/7175
Graphical Abstract