Neurosteroid allopregnanolone reduces ipsilateral visual cortex potentiation following unilateral optic nerve injury

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Abstract

In adult mice with unilateral optic nerve crush injury (ONC), we studied visual response plasticity in the visual cortex following stimulation with sinusoidal grating. We examined visually evoked potentials (VEP) in the primary visual cortex ipsilateral and contralateral to the crushed nerve. We found that unilateral ONC induces enhancement of visual response on the side ipsilateral to the injury that is evoked by visual stimulation to the intact eye. This enhancement was associated with supranormal spatial frequency thresholds in the intact eye when tested using optomotor response. To probe whether injury-induced disinhibition caused the potentiation, we treated animals with the neurosteroid allopregnanolone, a potent agonist of the GABAA receptor, one hour after crush and on post-injury days 3, 8, 13, and 18.

Allopregnanolone diminished enhancement of the VEP and this effect was associated with the upregulated synthesis of the δ-subunit of the GABAA receptor. Our study shows a new aspect of experience-dependent plasticity following unilateral ONC. This hyper-activity in the ipsilateral visual cortex is prevented by upregulation of GABA inhibition with allopregnanolone. Our findings suggest the therapeutic potential of allopregnanolone for modulation of plasticity in certain eye and brain disorders and a possible role for disinhibition in ipsilateral hyper-activity following unilateral ONC.

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