The iCre-DTA176 Mouse Exhibits Canonical Spontaneous Network Activity Associated With Retinal Degeneration

Spontaneous rhythmic activity is a defining feature of degenerating retinas and poses a major barrier to effective vision restoration. In this study, we sought to determine the presence, underlying mechanisms and functional consequences of spontaneous network activity in the Rho-iCre-DTA176 mouse, a novel model of retinal degeneration.

Extracellular recordings were obtained from isolated retinas using multielectrode arrays to characterize spontaneous and optogenetically evoked retinal ganglion cell (RGC) activity. Network mechanisms were probed pharmacologically by disrupting electrical coupling using the gap-junction blocker meclofenamic acid (MFA).

Retinal ganglion cells in Rho-iCre-DTA176 retinas exhibited pronounced oscillatory burst firing characterized by short interspike intervals, high burst occupancy and narrowband spectral structure. MFA selectively reduced short interspike intervals and abolished rhythmic bursting activity while sparing residual spontaneous spiking, thus supporting a network-driven origin of the aberrant activity. At the functional level, suppressing spontaneous oscillations significantly improved the signal-to-noise ratio of optogenetically evoked responses.

These results demonstrate that pathological retinal oscillations in the Rho-iCre-DTA176 mouse are driven by gap-junction-dependent network mechanisms and closely resemble those observed in established retinal degeneration models. Together, the results validate the Rho-iCre-DTA176 mouse as a valuable retina degeneration model for evaluating strategies aimed at restoring visual function.