The role of GluA1 in ocular dominance plasticity in the mouse visual cortex

Abstract

Ocular dominance plasticity is a widely studied model of experience-dependent cortical plasticity. It has been shown that potentiation of open eye responses resulting from monocular deprivation relies on a homeostatic response to loss of input from the closed eye, but the mechanisms by which this occurs are not fully understood. The role of GluA1 in the homeostatic component of ocular dominance (OD) plasticity has not so far been tested. In this study, we tested the idea that the GluA1 subunit of the AMPA receptor is necessary for open eye potentiation. We found that open eye potentiation did not occur in GluA1 knock-out (GluA1(-/-)) mice but did occur in wild-type littermates when monocular deprivation was imposed during the critical period. We also found that depression of the closed eye response that normally occurs in the monocular as well as binocular zone is delayed, but only in the monocular zone in GluA1(-/-) mice and only in a background strain we have previously shown lacks synaptic scaling (C57BL/6OlaHsd). In adult mice, we found that OD plasticity and facilitation of OD plasticity by prior monocular experience were both present in GluA1(-/-) mice, suggesting that the GluA1-dependent mechanisms only operate during the critical period.

Figure 1.

ISI methodology and transmission of visual information in GluA1^−/− mice (OlaHsd background). A, Top, Schematic of the ISI setup. Below, The deprivation and imaging timeline. B, Representative activity maps of WT and GluA1^−/−OlaHsd mice for monocular stimulation of the contralateral and ipsilateral eye. Scale bar, 500 μm. C, ERG waveforms under photopic (black) and scotopic (gray) conditions. D, B-wave amplitude under photopic and scotopic conditions (in μV, mean ± SEM). There was no effect of genotype (photopic: t = 0.12, p = 0.27; scoptopic: t = 0.53, p = 0.61). E, Example VEP traces from WT and GluA1^−/−OlaHsd mice, showing contralateral (black) and ipsilateral (gray) responses. F, Average maximum field potential amplitudes of WT mice and GluA1^−/−OlaHsd littermates. There was no effect of genotype (contralateral eye: t = 0.19, p = 0.84; ipsilateral eye: t = 0.04, p = 0.97).

Figure 2.

In C57BL/6OlaHsd mice, open eye depression is delayed but not abolished in the monocular zone in the GluA1^−/− genotype. ISI response magnitudes before and after MD for WT (black line) and GluA1^−/− (gray line) mice. A, Binocular zone response to contralateral eye stimulation. B, Binocular zone response to ipsilateral eye stimulation. C, Monocular zone response to contralateral eye stimulation. D, Ocular dominance index. Note baseline responses (control, left-most points) are significantly different (A–C). Note also that depression is delayed for the MZ but not BZ in GluA1^−/− mice (**p < 0.01; black, WT comparisons; gray, GluA1^−/− unpaired t tests). All absolute response magnitudes are mean ΔR/R values of the magnitude ×10⁻⁴ ± SEM (WT: control, n = 12; 3 d MD, n = 13; 5–6 d MD, n = 6; GluA1^−/−: control, n = 9, 3 d MD, n = 7; 5–6 d MD, n = 5). E, Example response isoazimuth maps to full field stimulation for binocular viewing (left) and monocular viewing (right) through the ipsilateral eye only. Note that response magnitudes are normalized to maximum as measured on the binocular viewing map. (M, medial; A, anterior). F, Green-light image illustrating location of MZ and BZ generated from the thresholded functional maps in E and F. Scale bars, 1 mm. G, Quantification of visual drive to binocular and monocular areas under binocular (black) and monocular (gray bars) stimulation for 6 WT-OlaHsd mice.

Figure 3.

In C57BL/6 mice, open eye potentiation is impaired in GluA1^−/− genotype. A, Binocular zone response to contralateral eye stimulation. B, Binocular zone response to ipsilateral eye stimulation. C, Monocular zone response to contralateral eye stimulation. D, Ocular dominance index. Response magnitudes before and after MD for WT-6J (black line) and GluA1^−/−6J (gray line) mice. Note that depression occurs normally after 3 d MD in the GluA1^−/−6J mice but the modest response recovery in WTs at 5–6 d in the closed eye response is clearly absent in GluA1^−/− mice (A) and there is no potentiation of the open eye response (B). WT: control, n = 7; 3 d MD, n = 7; 5–6 d MD, n = 6; GluA1^−/−6J: control, n = 7; 3 d MD, n = 7; 5–6 d MD, n = 7. Vertical brackets refer to comparisons between genotypes (t tests) and horizontal brackets within genotype but between time points. *p < 0.05, **p < 0.01; black, WT comparisons; gray, GluA1^−/− (unpaired t tests).

Figure 4.

Studies of adult plasticity in WT (black) and GluA1^−/− (gray) mice after a conditioning monocular deprivation during the critical period (OlaHsd background). In all cases, we found a large effect of opening or closing the ipsilateral eye, but no difference between genotypes. The control and first MD time points show the effect of a conditioning 7 d MD period in adulthood (ANOVA: effect of deprivation, t = 6.68, p < 0.0001; no effect of genotype, t = 0.43, p = 0.68, unpaired comparison, WT: control, n = 12; 3 d MD, n = 13; GluA1^−/−: control, n = 9; 3 d MD, n = 7). The second, third, and fourth time points show the effect of 4 weeks recovery followed by a second 3 d MD period. Once again, we found no differences between genotypes (ANOVA: no effect of genotype, t = 1.58, p = 0.22; effect of monocular/binocular vision, t = 20.08, p < 0.0001). Comparison of the second and third time point (same animals) show the recovery produced by restoring binocular vision (WT: t = 8.39, p < 0.0004; GluA1^−/−: t = 5.5, p < 0.01, paired t tests). Comparison of the third and final time point (same animals) show the effect of 3 d MD, which normally has no effect in a naive adult animal (open circle data point near control data at the left), but does cause a shift in ODI following a conditioning MD during the critical period (WT: t = 2.37, p < 0.05; GluA1^−/−: t = 4.41, p < 0.001, paired t tests). Note that for adult experiments, WT control n = 5, while six animals were imaged repeatedly for the remainder of the time points; GluA1^−/−OlaHsd control n = 4, while five animals were imaged repeated for the remainder of the time points. ***p < 0.001, **p < 0.01; *p < 0.05.