Compensatory responses to glaucoma pathology in the dorsolateral geniculate nucleus

Abstract

Glaucoma disrupts the conveyance of retinal signals to visual regions of the brain such as the dorsolateral geniculate nucleus (dLGN) due to degeneration of retinal ganglion cells (RGCs) and their axons. Although plasticity during development allows altered visual experience to modulate dLGN synapses and excitability, evidence for experience-dependent dLGN plasticity in adults is limited. However, glaucoma might trigger compensatory plasticity in adult dLGN, thereby compensating for diminished RGC synaptic drive. Here, we tested this using aged (11-15 month-old) DBA/2J mice, which develop high intraocular pressure and glaucoma. In brain slice recordings, we found that diminished RGC inputs could drive robust action potential firing in dLGN relay neurons that was comparable to controls. This was accompanied by increased intrinsic excitability and decreased magnitude of sustained inhibitory currents from GABA spillover to extrasynaptic receptors. These results implicate multiple cellular and synaptic mechanisms that support signaling despite the diminished RGC inputs in glaucoma. HIGHLIGHTSO_LIRetinogeniculate synapse strength in the dLGN is diminished in the DBA/2J mouse model of glaucoma C_LIO_LIDespite a loss of synaptic strength, retinogeniculate synapses drive robust action potential firing in dLGN relay neurons, suggestive of homeostatic compensation C_LIO_LIdLGN relay neurons from DBA/2J mice have an increase in intrinsic excitability, supporting action potential generation C_LIO_LIReduced extrasynaptic sustained inhibition in DBA/2J dLGN relay neurons can also support synaptically driven action potential firing C_LI