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Elena G. Sergeeva, Claudia Espinosa-Garcia, Machelle T Pardue, Donald G. Stein; Unilateral optic nerve crush induces potentiation of visual evoked response through the non-damaged eye in adult mice. Invest. Ophthalmol. Vis. Sci. 2016;57(12):606.
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We studied stimulus-selective response potentiation to demonstrate experience-dependent plasticity in adult mice following unilateral optic nerve crush (ONC). We hypothesized that the evoked response in the binocular area of the primary visual cortex of the contralateral, intact eye would be enhanced, and that allopregnanolone (ALLO), a putative GABAA receptor agonist, would diminish this potentiation.
Seven-week-old C57BL/6J mice were implanted with electrodes in the binocular visual cortices and randomly assigned to one of 4 groups: ONC/Veh, ONC/ALLO, Sham/Veh, Sham/ALLO (N=8/group). The left optic nerves were crushed in the ONC groups, and briefly exposed but left intact in the Sham groups. ALLO (10 mg/kg) or vehicle was given 1 hour after ONC and then on post-injury day (dpi) 3, 8, 13, and 18. Visual evoked potentials (VEP) were recorded before ONC (Baseline, BL) and on dpi 2, 7, 12, 17, 22 and 30. Visual stimuli consisted of horizontal or vertical full-field 100% contrast sine wave gratings (0.05 c/deg). Visual spatial frequency was assessed at BL and dpi 2, 6, 11, 16, 21 and 29 using an optokinetic tracking system. Two-way ANOVA with Bonferroni post-hoc correction was applied.
VEP amplitude was significantly augmented in all groups on dpi 2 (146±6.4% of BL), particularly in ONC animals, and slowly enhanced through dpi 30 (171±9.2%, p<0.0001). However, after dpi 12, while the VEP amplitude increased from 156 to 197% in the ONC/Veh group, in ONC/ALLO it stopped increasing and on day 30 was at the same level (148%) as Sham (difference ONC/Veh vs ONC/ALLO, p=0.003, Fig.1). Interestingly, in contrast to VEP amplitudes, the spatial frequency in the non-damaged eye in ONC/ALLO mice increased more than in ONC/Veh (BL 0.42±0.01 vs 0.44±0.02; dpi 2: 0.57±0.02 vs 0.52±0.02; dpi 29: 0.50±0.02 vs 0.46±0.02 c/deg; p<0.001, Fig.2).
Unilateral ONC enables enhancement of response potentiation in the visual cortex through the contralateral, non-damaged pathway. ALLO reduced this potentiation, possibly through GABAA-mediated inhibition, yet increased visual performance in the ONC/ALLO group. The contradictory dynamics of VEP and visual function after dpi12 suggests an optimal level of potentiation for functional improvement. Further studies to reveal the molecular mechanisms underlying the described potentiation will be implemented.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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