Early Visual Experience Shapes Binocularity in the Mouse Thalamocortical Pathway

Abstract

Monocular deprivation (MD) during the juvenile critical period leads to long-lasting impairments in binocular function and visual acuity. The site of these changes has been widely considered to be cortical. However, recent evidence indicates that binocular integration may first occur in the dorsolateral geniculate nucleus of the thalamus (dLGN), raising the question of whether MD during the critical period may produce long-lasting deficits in dLGN binocular integration. Using in vivo two-photon Ca2+ imaging of dLGN afferents and excitatory neurons in superficial layers of primary visual cortex (V1), we demonstrate that critical-period MD leads to a persistent and selective loss of binocular dLGN inputs, while leaving spatial acuity in the thalamocortical pathway intact. Despite being few in number, binocular dLGN boutons display remarkably robust visual responses, on average twice stronger than monocular boutons, and their responses are exquisitely well-matched between the eyes. To our surprise, we found that MD leads to a profound binocular mismatch of response amplitude, spatial frequency and orientation tuning detected at the level of single thalamocortical synapses. In comparison, V1 neurons display deficits in both binocular integration and spatial acuity following MD. Our data provide the most compelling evidence to date demonstrating that following critical-period MD, binocular deficits observed at the level of V1 may at least in part originate from dLGN binocular dysfunction, while spatial acuity deficits arise from cortical circuits. These findings highlight a hitherto unknown role of the thalamus as a site for developmental refinement of binocular vision.