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J Neurosci. 2019 Mar 13. pii: 3188-18. doi: 10.1523/JNEUROSCI.3188-18.2019. [Epub ahead of print]

Homer1a is required for establishment of contralateral bias and maintenance of ocular dominance in mouse visual cortex.

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The Zanvyl-Krieger Mind/Brain Institute, Johns Hopkins University, Baltimore, MD 21218, USA.
Cell Molecular Developmental Biology and Biophysics (CMDB) Graduate Program, Johns Hopkins University, Baltimore, MD 21218, USA.
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
The Zanvyl-Krieger Mind/Brain Institute, Johns Hopkins University, Baltimore, MD 21218, USA
The Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD 21218, USA.


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 towards 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 due to 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 days) monocular deprivation (MD) of the contralateral eye with lid suture. However, unlike wildtype counterparts, H1a KOs continued to shift OD index with a longer duration (5-6 days) 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.SIGNIFICANCE STATEMENTVisual cortical neurons display varying degree of responsiveness to visual stimuli through each eye, which determines their ocular dominance (OD). Molecular mechanisms responsible for establishing normal OD are largely unknown. Development of OD has been shown to be largely independent of visual experience, but guided by molecular cues and spontaneous activity. We found that activity-dependent immediate early gene H1a is critical for establishing normal OD in V1 of mice, which show contralateral eye dominance. Despite the weaker contralateral bias, H1aKOs undergo largely normal OD plasticity. The basic phenotype of H1aKO was recapitulated by mGluR5 mutation that severely reduces H1a interaction. Our results suggest a novel role of mGluR5-H1a interaction in strengthening contralateral eye inputs to V1 during postnatal development.

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