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

Abstract

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 knockout (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.

Ocular dominance plasticity: Molecular mechanisms revisited

“…Another curious set of findings are that the suggested homeostatic role of Homer 1a (an immediately early gene) in establishing the innate contralateral eye bias in mice is independent of visual experience, but necessary for OD changes in the long-term (5-6 days) MD and unnecessary for the short-term (2-3 days) MD effects (Choski, Druciak, Worley, & Lee, 2019). It must be pointed out that in mice, the duration of MD for 4 days or longer is usually needed for the clear and thus stable changes in the OD distribution (Gordon & Stryker, 1996; see also Table 1).…”

“…In postsynaptic density (PSD)‐95 knock‐out mice, an instructive role of PSD‐95 in opening and closing the critical period was shown, as expressed in the maturation of “silent” glutamatergic synapses, largely independent of the inhibitory tone (Huang et al, 2015). Another curious set of findings are that the suggested homeostatic role of Homer 1a (an immediately early gene) in establishing the innate contralateral eye bias in mice is independent of visual experience, but necessary for OD changes in the long‐term (5–6 days) MD and unnecessary for the short‐term (2–3 days) MD effects (Choski, Druciak, Worley, & Lee, 2019). It must be pointed out that in mice, the duration of MD for 4 days or longer is usually needed for the clear and thus stable changes in the OD distribution (Gordon & Stryker, 1996; see also Table 1).…”

Astrocytic glutamate uptake coordinates experience-dependent, eye-specific refinement in developing visual cortex

“…It is possible that distinct cellular mechanisms differentially regulate contralateral and ipsilateral responses and plasticity. For example, it has recently been shown that Homer1a specifically and actively establishes the contralateral bias intrinsic to binocular-responsive cells (Chokshi et al, 2019). Our work indicates that ipsilateral response depression may be more susceptible to changes in GLT1-mediated glutamate uptake.…”

Astrocyte glutamate uptake coordinates experience‐dependent, eye‐specific refinement in developing visual cortex

“…Therefore, future work will be needed to clarify the mechanisms relating developmental synaptic refinement to particular subsets of synapses, the role of astrocytes and GLT1, and the microstructure of the tripartite synapse. (Chokshi, Druciak, Worley, & Lee, 2019). Our work indicates that ipsilateral response depression may be more susceptible to changes in GLT1-mediated glutamate uptake.…”

“…It is possible that distinct cellular mechanisms differentially regulate contralateral and ipsilateral responses and plasticity. For example, it has recently been shown that Homer1a specifically and actively establishes the contralateral bias intrinsic to binocular‐responsive cells (Chokshi, Druciak, Worley, & Lee, 2019). Our work indicates that ipsilateral response depression may be more susceptible to changes in GLT1‐mediated glutamate uptake.…”