Differential impact of retinal lesions on visual responses of LGN X and Y cells

Abstract

Damage to retinal cells from disease or injury causes vision loss and remodeling of downstream visual information processing circuits. As retinal cell replacement therapies and prosthetics become increasingly viable, we must understand post-retinal consequences of retinal cell loss to optimally recover visual perception. Here, we asked whether loss of retinal ganglion cells (RGCs) differentially impacts postsynaptic neurons in the visual thalamus - the dorsal lateral geniculate nucleus (LGN) - of ferrets, highly visual carnivores. We hypothesized that RGC loss might impact X more than Y LGN neurons, as there is less divergence in X retinogeniculate connections. We induced excitotoxic lesions of RGCs in a single eye and recorded neurophysiological responses of both contra- and ipsi-lesional LGN neurons to a variety of visual stimuli. We observed loss of responses among many LGN neurons, presumably with receptive fields within the scotoma. We also observed contralesional LGN neurons with receptive fields within or at the border of the scotoma that responded consistently to drifting sinusoidal gratings and spatiotemporally dynamic stimuli, enabling their classification as X or Y cells. Contralesional Y cell responses remained intact while contralesional X cells demonstrated higher firing rates, altered tuning to stimulus contrast and temporal frequency, and reduced spike timing precision. Consistent with neurophysiological results, alpha RGCs appeared relatively spared compared to beta RGCs. Together, our findings show that retinal cell loss differentially impacts downstream neuronal circuits, suggesting that supplemental vision recovery therapies may need to target visual circuits specialized for acuity vision.

Significance Statement Vision loss from damage to retinal neurons may be partially ameliorated by improving cell replacement therapies and retinal prosthetics. However, retinal cell loss likely causes remodeling of circuits downstream, e.g., in the visual thalamus, which may also require treatment to restore natural visual perception. We studied neurophysiological changes in the visual thalamus, immediately postsynaptic to retina, following excitotoxic lesions of retinal output neurons. We discovered disproportionate effects on thalamic cell types, whereby cells receiving divergent retinal inputs were spared and those with few-to-one inputs had altered, noisier responses. Our findings suggest that supplemental vision therapies may need to target specific visual pathways to optimize acuity vision.