Monocular deprivation in adult mice alters visual acuity and single-unit activity

Abstract

It has been discovered recently that monocular deprivation in young adult mice induces ocular dominance plasticity (ODP). This contradicts the traditional belief that ODP is restricted to a juvenile critical period. However, questions remain. ODP of young adults has been observed only using methods that are indirectly related to vision, and the plasticity of young adults appears diminished in comparison with juveniles. Therefore, we asked whether the newly discovered adult ODP broadly reflects plasticity of visual cortical function and whether it persists into full maturity. Single-unit activity is the standard physiological marker of visual cortical function. Using a more optimized protocol for recording single-units, we find evidence of adult ODP of single-units and show that it is most pronounced in deep cortical layers. Furthermore, using visual evoked potentials (VEP), we find that ODP is equally robust in young adults and mature adults and is observable after just one day of monocular deprivation. Finally, we find that monocular deprivation in adults changes spatial frequency thresholds of the VEP, decreasing the acuity of the deprived pathway and improving the acuity of the non-deprived pathway. Thus, in mice, the primary visual cortex is capable of remarkable adaptation throughout life.

Figure 1.

Ocular dominance plasticity can be demonstrated by single-unit recordings in urethane anesthetized young adult mice (P55–P110). (A) Ocular dominance histograms for each hemisphere of non-deprived mice (188 cells, five mice), and MD mice (213 cells, six mice). Category 1 cells were driven exclusively by the contralateral eye, category 7 cells were driven exclusively by the ipsilateral eye, and category 4 cells were driven equally by both eyes. UC, uncharacterized; ND, non-deprived; MD, monocularly deprived (for 4 or 9 d); Left Hem, left hemisphere; Right Hem, right hemisphere; Contra Hem, hemisphere contralateral to the deprived eye; Ipsi Hem, hemisphere ipsilateral to the deprived eye. (B) CBI scores calculated (see Materials and Methods) for each hemisphere in each mouse. Open triangles/squares represent the CBIs for the left/right hemisphere of individual non-deprived mice. Filled squares/triangles represent the CBIs for the hemisphere ipsilateral/contralateral to the deprived eye of individual MD mice. MD4, MD for four days; MD9, MD for nine days. (C) The average CBI for each hemisphere in non-deprived and MD mice. Asterisks (*) indicate a significant difference between the non-deprived hemispheres (n = 10) and the hemispheres contralateral (n = 6) or ipsilateral (n = 6) to the deprived eye (P < 0.005, Bonferroni post-hoc tests). LH, left hemisphere; RH, right hemisphere; CH, hemisphere contralateral to the deprived eye; IH, hemisphere ipsilateral to the deprived eye. Error bars indicate SEM.

Figure 2.

Retinotopy, topographic sampling, and visual responsiveness were similar in non-deprived and MD young adult mice (P55–P110). (A) Regression plots of receptive field azimuth vs. lateromedial electrode position were used to assess retinotopy and topographic sampling in non-deprived mice (30 penetrations, five mice) and MD mice (36 penetrations, six mice). The ordinate shows degrees of azimuth relative to the vertical meridian, while the abscissa indicates distance from the lateral edge of V1b (see Materials and Methods). (B) CBI plotted as a function of azimuth. Azimuth was binned in the following groups: 2.5° midpoint (represents azimuth data from −1° to 7°), 11.5° midpoint (represents azimuth data from 8° to 16°), and 20.5° midpoint (represents azimuth data from 17° to 25°). Open symbols with dotted lines depict data in MD mice, while filled symbols and solid lines show data in non-deprived mice. IH, hemisphere ipsilateral to the deprived eye; LH, left hemisphere of non-deprived mice; RH, right hemisphere of non-deprived mice; CH, hemisphere contralateral to the deprived eye. (C) Average response strength and signal-to-noise ratio (see Materials and Methods) in each hemisphere of non-deprived and MD mice. Error bars indicate SEM.

Figure 3.

ODP is primarily expressed in the deep layers of V1 in young adult mice (P60–P106). (A) Micrograph showing electrolytic lesion sites for a penetration in V1b. Arrows with numbers indicate lesion sites and their cortical depths (in microns). 2/3, layers 2/3; 4, layer 4; 5, layer 5; 6, layer 6; WM, white matter. Scale bar = 200 μm. Dorsal is at the top and lateral is to the right of the figure. (B) The average contralateral bias index (CBI, see Materials and Methods) of cells pooled for the indicated cortical depths (10–24 cells/bin) in five MD young adult mice (P60–P106). (C) The average CBI of cells pooled for cortical depths ≤450 μm (S, superficial layers) or >450 μm (D, deep layers) in five non-deprived (n = 10 hemispheres) and five MD mice (n = 5 hemispheres contralateral to the deprived eye, and 5 hemispheres ipsilateral to the deprived eye). The asterisk (*) denotes a significant difference between superficial and deep layers (hemisphere × layer interaction, P < 0.03, two-factor ANOVA). Error bars indicate SEM.

Figure 4.

The VEP signal, but not noise, varied with both spatial frequency and contrast. Spatial frequency sweep data for the left hemisphere of a single non-deprived adult (P180) mouse. The VEP signal (top panels) and noise (bottom panels) are shown as a function of spatial frequency and grating contrast. The spatial frequencies (in cycles/degree) used were: 0.50, 0.39, 0.30, 0.23, 0.18, 0.14, 0.11, 0.084, 0.065, 0.050 (note: spatial frequency sweeps for this animal did not include stimuli at 0.65 cycles/degree). The visual stimuli were presented at five different contrasts (color-coded, see inset). Each curve is the average of 16 sweeps. L Hem, left hemisphere; L Eye, left eye; R Eye, right eye.

Figure 5.

MD strongly alters swept spatial frequency curves in mature adult mice (P181–P390). (A,B) Averaged normalized VEP amplitudes are shown as a function of spatial frequency and contrast for non-deprived (A) and four-day right eye MD (B) mature adult mice. VEPs were elicited by using a contrast grating stimulus that swept from 0.65 to 0.05 cycles/degree. Five different contrast levels were used, 5.5%, 11%, 22%, 44%, and 88% (color-coded, see insets). The right and left hemispheres were recorded simultaneously while either the right or left eye was stimulated; results for the crossed and uncrossed pathways of each eye are shown. The ordinate shows the amplitude normalized to a scaling factor for the hemisphere (see Materials and Methods). Each curve represents the average of 10 animals. Error bars indicate SEM.

Figure 6.

Ocular dominance plasticity is equally robust in young adult (P90–180) and mature adult (>P180) mice. We represented the ocular dominance of each hemisphere in each mouse using an ocular dominance index (ODI, see Materials and Methods). (A) ODIs (ordinate) for the left (filled symbols) and right (open symbols) hemispheres of non-deprived mice (top) or four-day right eye MD mice (bottom) as a function of age at the time of recording (abscissa). ODIs were calculated using data obtained at 88% contrast and a spatial frequency of 0.05 cycles/degree. Each data point represents a single hemisphere. (B) The average ODI for each hemisphere of non-deprived and MD mice for juveniles (P26–P36, five mice), young adults (P90–P180, five mice), and mature adults (>P180, 10 mice). The asterisk and bar indicate that there was an overall hemispheric difference in the MD groups (hemisphere × deprivation interaction, P < 0.005, three-way ANOVA). Error bars indicate SEM.

Figure 7.

Adult ODP demonstrated by VEP has a rapid onset. The average ODI is shown for each hemisphere of mice which were non-deprived (ND, 13 mice) or right eye deprived for: one day (MD1, four mice), two days (MD2, six mice), four days (MD4, 12 mice), or nine days (MD9, three mice). All mice were maintained on a 12-h light/12-h dark cycle, except MD1 mice which were housed in continuous light for 24 h. Error bars indicate SEM.

Figure 8.

MD alters the visual acuity of the uncrossed (ipsilateral) pathway in adult mice (P90–P390). (A) Spatial frequency threshold (highest spatial frequency that produces a response above criterion) is shown as a function of contrast of the grating stimulus for non-deprived (top) and 4-d right eye MD mice (bottom). Each point is the mean of 11–15 hemispheres. Error bars indicate SEM. (B) Acuity indexes (the average of spatial frequency thresholds at 22%, 44%, and 88% contrast) are shown for the uncrossed and crossed pathways of each eye (each value is the average of 13–15 hemispheres). Asterisk (*) indicates a significant difference between non-deprived and MD groups (P ≤ 0.03, Bonferroni post-hoc test). Error bars indicate SEM.

Figure 9.

VEP waveforms in a monocularly deprived mouse. VEPs were recorded from the right and left hemisphere of a mouse following monocular deprivation of the right eye. The visual stimulus was a reversal grating presented at a fixed contrast of 80% for a duration of 10 sec. The grating reversed contrast at a frequency of 2 Hz. The stimulus was presented alternately to the right and left eye for a total of four trials each. L hem, left hemisphere; R hem, right hemisphere; L eye, left eye; R eye, right eye.