Homer1a Is Required for Establishment of Contralateral Bias and Maintenance of Ocular Dominance in Mouse Visual Cortex

It is well established across many species that neurons in the primary visual cortex (V1) display preference for visual input from one eye or the other, which is termed ocular dominance (OD). In rodents, V1 neurons exhibit a strong bias toward the contralateral eye. Molecular mechanisms of how OD is established and later maintained by plastic changes are largely unknown. Here we report a novel role of an activity-dependent immediate early gene Homer1a (H1a) in these processes. Using both sexes of H1a knock-out (KO) mice, we found that there is basal reduction in the OD index of V1 neurons measured using intrinsic signal imaging. This was because of a reduction in the strength of inputs from the contralateral eye, which is normally dominant in mice. The abnormal basal OD index was not dependent on visual experience and is driven by postnatal expression of H1a. Despite this, H1a KOs still exhibited normal shifts in OD index following a short-term (2-3 d) monocular deprivation (MD) of the contralateral eye with lid suture. However, unlike wild-type counterparts, H1a KOs continued to shift OD index with a longer duration (5-6 d) of MD. The same phenotype was recapitulated in a mouse model that has reduced Homer1 binding to metabotropic glutamate receptor 5 (mGluR5). Our results suggest a novel role of H1a and its interaction with mGluR5 in strengthening contralateral eye inputs during postnatal development to establish normal contralateral bias in mouse V1 without much impact on OD shift with brief MD.