Enhancement of vision by monocular deprivation in adult mice

Abstract

Plasticity of vision mediated through binocular interactions has been reported in mammals only during a "critical" period in juvenile life, wherein monocular deprivation (MD) causes an enduring loss of visual acuity (amblyopia) selectively through the deprived eye. Here, we report a different form of interocular plasticity of vision in adult mice in which MD leads to an enhancement of the optokinetic response (OKR) selectively through the nondeprived eye. Over 5 d of MD, the spatial frequency sensitivity of the OKR increased gradually, reaching a plateau of approximately 36% above pre-deprivation baseline. Eye opening initiated a gradual decline, but sensitivity was maintained above pre-deprivation baseline for 5-6 d. Enhanced function was restricted to the monocular visual field, notwithstanding the dependence of the plasticity on binocular interactions. Activity in visual cortex ipsilateral to the deprived eye was necessary for the characteristic induction of the enhancement, and activity in visual cortex contralateral to the deprived eye was necessary for its maintenance after MD. The plasticity also displayed distinct learning-like properties: Active testing experience was required to attain maximal enhancement and for enhancement to persist after MD, and the duration of enhanced sensitivity after MD was extended by increasing the length of MD, and by repeating MD. These data show that the adult mouse visual system maintains a form of experience-dependent plasticity in which the visual cortex can modulate the normal function of subcortical visual pathways.

Figure 1.

Effect of 5 d MD (shading) on OKR sensitivity. A, Spatial frequency sensitivity through nondeprived eyes (open; top trace) was increased and reached a maximum over 3–4 d of MD. Opening the deprived eye initiated a gradual decline to baseline over 5–6 d. Deprived eye responses (closed; bottom trace) were not affected after the first day. B, Effect of MD on contrast sensitivity was similar: Sensitivity increased from baseline (open squares) over 5 d of MD (day 5 plotted with closed circles) and returned to baseline levels over 10 d (open diamonds; plotted is the 10th day after MD). C, There was little effect of MD on contrast sensitivity through the deprived eye (pre-deprivation baseline, open squares; immediately after day 5 of MD, closed circles; 10 d after MD, open diamonds). ±SEM plotted with vertical scale lines are present but are often occluded by data symbols in this and other figures.

Figure 2.

Selective visual field responses in schematic illustration. The length of arching arrows represent the segment of the visual field in which the grating was present during testing (binocular field, Binocular; monocular field, Monocular), and the associated numbers represent spatial frequency thresholds in c/d (see Materials and Methods for details). A, In experimentally naive mice, full-field (outside arrow; dotted segment represents the region of the field not visible to the eyes) stimulation generated a threshold of 0.39 c/d. Limiting the stimulus to the binocular field resulted in the same threshold as full-field stimulation (0.39 c/d); monocular-field responses (0.34 c/d) were lower regardless of the size of the stimulus within the field. Combining monocular and binocular stimulation resulted in the same threshold (0.39 c/d) as binocular alone or full-field stimulation. B, Full-field stimulation in enhanced mice resulted in a threshold of 0.55 c/d. Monocular field stimulation alone or combined with binocular resulted in about the same threshold (0.54 c/d), whereas binocular responses alone did not differ (0.39 c/d) from those in naive animals (A).

Figure 3.

Experiential control of enhanced spatial frequency sensitivity. For comparison, the dashed trace is nondeprived eye profile from Figure 1A. A, Sensitivity measured through the nondeprived eye (top trace), but not tested during 5 d MD (shading; closed circles), did not reach maximal enhancement, and sensitivity dropped to baseline immediately on eye opening. Deprived eye responses (bottom trace) were affected little by MD. B, Ten-day MD without testing produced comparable results. C, Animals tested twice daily during a 5 d MD presented a similar profile of enhancement as that in animals tested only once daily (dotted trace), but the rate of enhancement in sensitivity during MD was slightly slower, as was the rate of decay in sensitivity after MD. D, BD for 5 d had little effect on thresholds measured through either eye. E, The intact eye (top trace) after monocular enucleation (bottom trace) was enhanced by 10% after 1 d, and remained at that level thereafter. Occlusion of the eye for 5 d (shading) had no effect on the threshold.

Figure 4.

Effect of visual cortex manipulations on enhancement induced by 5 d MD. A, Bilateral aspiration of visual cortex. Left panel, Schematic representation of deprived (shaded box) and nondeprived eyes combined with superimposed drawings of the brains showing the location of lesions. Right panel, For comparison, the dashed trace is nondeprived eye profile from Figure 1A. The spatial frequency threshold through the nondeprived eye of animals with bilateral V1 lesions (top trace) became slightly elevated (∼10%) during the MD (gray box) and dropped to baseline immediately on eye opening. Sensitivity through the deprived eye (bottom trace) was not affected by the treatment. B, C, Unilateral inactivation of visual cortex. Period during that muscimol-releasing Elvax was present is indicated in black; period of MD is indicated in gray. Sensitivity measured before surgery was stable at normal baseline levels, and muscimol-releasing Elvax did not affect sensitivity through either eye before MD. B, Inactivating visual cortex ipsilateral to the deprived eye blocked the characteristic enhancement of sensitivity (closed circles). The effect of silencing was reversible, however, because MD after removal of the muscimol-impregnated Elvax resulted in characteristic enhancement. Elvax implants without muscimol presented a profile of enhancement characteristic of that in nontreated animals (indicated by dotted line in both panels). C, Inactivation of visual cortex contralateral to the deprived eye, and controls. MD induced an enhancement of OKRs characteristic of that in animals with control Elvax; however, sensitivity dropped to baseline as soon as the deprived eye was opened. Removal of the muscimol-impregnated Elvax enabled a subsequent MD to enhance sensitivity in a characteristic manner. Deprived eye responses (bottom traces) were not affected by MD in either experiment.

Figure 5.

Effect on spatial frequency sensitivity of varying the duration of MD (indicated by shading). A, Three day MD resulted in enhancement through nondeprived eye (top trace) only during the deprivation. B, Five day MD resulted in enhanced responses that decremented gradually after MD; replication of experiment in Figure 1A. C, Ten day MD both extended the duration of enhanced responses after MD, and enabled enhanced sensitivity to persist at maximum. None of the above manipulations affected deprived eye responses (A–C, bottom traces). D, Detailed comparison of 3 d (open triangles), 5 d (closed circles), twice daily testing for 5 d (Fig. 3C, open circles) and 10 d (open squares) profiles after MD.

Figure 6.

Effect on spatial frequency sensitivity of repeating MD (shading). Traces in A–C are a continuation of those in Figure 5, A–C (represented with dotted lines). A, Repeating a 3 d period of MD resulted in a profile of enhancement through nondeprived eyes similar to that after the first MD. B, A second 5 d MD resulted in an immediate maximal enhancement that was maintained at maximal values and remained above baseline far longer than after the first MD. C, A second 10 d MD resulted in a profile similar to B, but enhanced responses were maintained even longer. Repeated MD did not affect deprived eye responses (A–C, bottom traces). D, Comparison of second 3, 5, and 10 d MD profiles after MD, in detail. E, Comparison of profiles after first (1) (Fig. 5C) second (2) (C), and third (3) periods of 10 d MD reveals increasing duration of enhancement. F, Two, 5 d periods of MD (2×5d; B) resulted in longer duration enhancement after MD than that after a single 10 d MD (10d) (Fig. 5C).