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Comparative Study
. 2010 Apr;13(4):450-7.
doi: 10.1038/nn.2508. Epub 2010 Mar 14.

Loss of Arc Renders the Visual Cortex Impervious to the Effects of Sensory Experience or Deprivation

Affiliations
Free PMC article
Comparative Study

Loss of Arc Renders the Visual Cortex Impervious to the Effects of Sensory Experience or Deprivation

Cortina L McCurry et al. Nat Neurosci. .
Free PMC article

Abstract

A myriad of mechanisms have been suggested to account for the full richness of visual cortical plasticity. We found that visual cortex lacking Arc is impervious to the effects of deprivation or experience. Using intrinsic signal imaging and chronic visually evoked potential recordings, we found that Arc(-/-) mice did not exhibit depression of deprived-eye responses or a shift in ocular dominance after brief monocular deprivation. Extended deprivation also failed to elicit a shift in ocular dominance or open-eye potentiation. Moreover, Arc(-/-) mice lacked stimulus-selective response potentiation. Although Arc(-/-) mice exhibited normal visual acuity, baseline ocular dominance was abnormal and resembled that observed after dark-rearing. These data suggest that Arc is required for the experience-dependent processes that normally establish and modify synaptic connections in visual cortex.

Conflict of interest statement

Competing interests statement: The authors declare that they have no competing financial interests.

Figures

Figure 1
Figure 1
Loss of Arc does not affect V1 responsiveness and organization. (a) Intrinsic signal imaging of V1 (left inset) in WT and Arc−/− mice. (Top) Ocular dominance map of V1, in a WT mouse (left) and an Arc−/− mouse (right); MZ=monocular zone, BZ=binocular zone. Scale at right illustrates binocularity index of pixels. Scale bar= 500 µm. V1 in Arc−/− mice is similar to that in WT mice in total area (WT n=6, area=1.401±0.07 mm2; Arc−/− n=10, area=1.270±0.15 mm2; p>0.5, t–test). (Bottom) Retinotopic organization of V1 in a WT mouse (left), and an Arc−/− mouse (right). Each image shows the mapping of elevation according to scale at top right. (b) Scatter analysis of 50×50 pixel area within white box in A, for WT and Arc−/− mice. The receptive field center (phase) difference between sets of 5 adjacent pixels is shown in histogram at right. The precision of local mapping is comparable between WT and Arc−/− mice.
Figure 2
Figure 2
Intrinsic signal imaging after monocular deprivation illustrates a requirement for Arc in deprived–eye depression after short–term monocular deprivation. (a) (Top) monocular deprivation was initiated near the peak of the critical period for 3–4 days. Control mice were age–matched to deprived mice. (Bottom) ODIs for individual mice are shown as circles. Closed circles depict control mice, open circles deprived mice. Horizontal bars represent group averages. (WT: control, n=9, ODI=0.28±0.03; deprived, n=14, ODI=–0.05±0.03, p<0.0001, t–test Arc−/−: control, n=10, ODI=0.19±0.02; deprived, n=11, ODI=0.13±0.02, p>0.1, t–test). (b) Response magnitude in WT mice driven by the contralateral eye (filled bars) and ipsilateral eye (open bars), plotted as average ΔR/R × 10−3. A depression in the contralateral eye response amplitude can be seen (control=2.9±0.27, deprived=1.62±0.23, *p<0.001, t–test). No change in the ipsilateral eye response is detected (control=1.56±.21, deprived=1.68±.19, p>0.8, t–test). (c) No change in contralateral (filled bar) response occurs in Arc−/− mice after deprivation (control=2.25±0.28, deprived=2.5±0.26, p>0.2, t–test); similarly, no change in ipsilateral (open bar) response is detected (control=1.35±0.23, deprived=1.64±0.19, p>0.2, t–test). (ΔR/R is the change in reflectance over baseline reflectance. Error bars represent SEM).
Figure 3
Figure 3
Chronic VEP recordings show that Arc−/− mice do not exhibit ocular dominance plasticity after short–term monocular deprivation. (a) WT mice exhibit a significant depression in contralateral (deprived eye) responses (n=11; Day 0=149±8.8 µV, 3 Day monocular deprivation=75.4±8.8 µV, *p< <0.0001, paired t–test). No significant change was observed in ipsilateral responses (n=11; Day 0=70.4±6.4 µV, 3 Day monocular deprivation=68.8±8 µV, p>0.8, paired t–test). Averaged waveforms across all mice are shown at top. (b) Arc−/− mice exhibit no changes in contralateral responses (n=8; Day 0=121±14.7 µV, 3 Day monocular deprivation=111.3±13.5 µV, p>0.2, paired t–test) or in ipsilateral responses (n=8; Day 0=92.5±15 µV, 3 Day monocular deprivation=85.8±10.7 µV, p>0.7, paired t–test). Averaged waveforms are shown at top. (c) WT mice exhibit a significant shift in the C/I ratio (n=11; Day 0=2.2±0.16, 3 Day monocular deprivation=1.2±0.16, *p<<0.0001, paired t–test), whereas Arc−/− mice exhibit no significant shift in the C/I ratio (n=8; Day 0=1.4±0.12, 3 Day monocular deprivation=1.5±0.33, p>0.8, paired t–test). Arc−/− mice exhibit a significantly smaller baseline C/I ratio than WT mice (WT n=11, C/I ratio 2.22±0.16; Arc−/− n=8, C/I ratio 1.37±0.12, #p<0.001, t–test). (Error bars represent SEM).
Figure 4
Figure 4
Arc is required for the decrease in surface AMPARs after short–term monocular deprivation. (a) Schematic of mouse brain showing the segments of V1 dissected for biochemical analysis. Since V1 is dominated by contralateral eye responses, cortex contralateral to the deprived eye was termed “deprived” while cortex ipsilateral to the deprived eye was treated as “control”. (b) Example immunoblots of total and biotinylated surface proteins in the visual cortex of Arc−/− and WT mice. Full blots are presented in Supplementary Figure 6. GAPDH was used as an internal control to show that biotin specifically labeled surface proteins. In addition, a control image (bottom) shows the specificity of the biotinylation assay. No band can be detected in the surface lane of protein sample not exposed to biotin. (c) Summary of changes in surface/total protein levels occurring after deprivation (WT, n=5; Arc−/−, n=7). Surface levels of GluR1 were significantly lower in the deprived hemisphere of WT mice compared to control (*p<.0001, t–test), but not in Arc−/− animals (p >0.2, t–test). Error bars represent SEM.
Figure 5
Figure 5
Arc−/− mice do not show a shift in ocular dominance after extended deprivation, as assessed by intrinsic signal imaging. (a) (Top) monocular deprivation was initiated near the peak of the critical period for 7 days. Control mice were age–matched to deprived mice. ODIs for individual mice are shown as circles. Closed circles depict control mice, open circles deprived mice. Horizontal bars represent group averages. (WT: control, n=9, ODI= 0.28±0.03; deprived, n=7, ODI=−0.063±0.02, p<0.0001; Arc−/−: control, n=10, ODI=0.19±0.02; deprived, n=8, ODI=0.13±.02, p=0.17). (b) Response magnitude in WT mice driven by the contralateral eye (filled bars) and ipsilateral eye (open bars), plotted as average ΔR/R × 10−3. Some, albeit not significant, depression in the contralateral eye response amplitude can be seen (control=2.9±0.27, deprived= 2.1±0.23, p>0.05). Lid suture results in an increase in the ipsilateral eye response (control=1.56±0.21, deprived=2.49±0.17, *p<0.05). (c) No change in contralateral (filled bar) response occurs in Arc−/− animals after deprivation (control=2.25±0.28, deprived= 2.2±0.21, p>0.6); similarly, no change in ipsilateral (open bar) response is detected (control=1.35±0.23, deprived=1.5±0.21, p>0.6). (ΔR/R is the change in reflectance over baseline reflectance. Error bars represent SEM. Statistical analyses for a–c conducted using one–way ANOVA with Bonferroni correction).
Figure 6
Figure 6
Arc−/− mice exhibit no ocular dominance plasticity as assessed by chronic VEP recordings after long–term monocular deprivation. (a) WT mice exhibit a significant depression in contralateral (deprived eye) responses (n = 7; Day 0=152±9.2 µV, 7 Day monocular deprivation = 89.5±11.5 µV, *p<0.003, paired t–test) and a significant potentiation in ipsilateral responses (n = 7; Day 0=84.9±9.8 µV, 7 Day monocular deprivation=114.2±10.1 µV, #p<0.05, paired t–test). Averaged waveforms are shown at top. (b) Arc−/− mice exhibit no changes in contralateral (n=6; Day 0=112±2.2 µV, 7 Day monocular deprivation=100±6 µV, p>0.1, paired t–test) or in ipsilateral responses (n=8; Day 0=96±8.6 µV, 3 Day monocular deprivation=84±10 µV, p>0.4, paired t–test). Averaged waveforms are shown at top (c) WT mice exhibit a significant shift in the C/I ratio (n=7; Day 0=1.9±0.14, 7 Day monocular deprivation=0.8±0.06, *p < 0.0001, paired t–test), whereas Arc−/− mice exhibit no significant shift in the C/I ratio (n=6; Day 0=1.2±0.1, 7 Day monocular deprivation=1.25±0.11, p>0.7, paired t–test). Arc−/− mice exhibit a significantly smaller baseline C/I ratio than WT mice (WT n=7, C/I ratio 1.87±0.14; Arc−/− n=6, C/I ratio 1.2±0.1, #p<0.003) (Error bars represent SEM).
Figure 7
Figure 7
Dark–rearing WT mice from birth mimics the contralateral to ipsilateral ratio observed Arc−/− mice. (a) Arc−/− and dark–reared (DR) mice exhibit a significant decrease in the C/I ratio in layer 4 VEPs as compared to WT mice (WT: n=16, 2.1 ±0.1; Arc−/−: n=16, 1.35±0.08, *p<<0.0001, t–test; DR: n=11, 1.29±0.1, *p << 0.0001, t–test). (b) The change in ocular dominance ratio in Arc−/− and DR mice is mainly due to a significant depression in contralateral (C) responses (WT: 146±6 µV; Arc−/−, 116±7 µV, *p<0.006, t–test; DR: 74 ±9 µV, *p<<0.0001, t–test) as ipsilateral responses (I) were not significantly different (WT: 72 ±5 µV; Arc−/−, 90±8 µV, p>0.07, t–test; DR: 59±8 µV, p>0.2, t–test). (Error bars represent SEM).
Figure 8
Figure 8
Arc−/− mice lack stimulus–selective response potentiation (SRP) whereas dark–reared mice exhibit enhanced SRP in V1. (a) WT mice exhibit large and sustained potentiation of binocular VEPs over many days of exposure to the same stimulus orientation (n=11). Responses to a control orthogonal stimulus (90°, open black circle) shown at day 6 were not significantly potentiated. Dark–reared mice have small VEPs at baseline, which become dramatically potentiated after exposure to the same stimulus orientation (n=12). Responses to a control orthogonal stimulus (90°, open red triangle) are significantly increased compared with baseline VEPs but are also significantly smaller than the SRP orientation at day 6. In contrast, Arc−/− mice exhibit no significant potentiation of responses to the same stimulus (n=16). Responses to the control orthogonal stimulus (90°, blue square) were also not significantly different from baseline, suggesting no general decrease in responses over time. (b) VEPs normalized to baseline values show that dark–reared mice exhibit a relative enhancement of potentiation as compared to light–reared mice, while Arc−/− mice show no relative potentiation of VEPs. (c) Average VEP waveforms at baseline (day 1) and after 5 days of repeated exposure to the same orientation (day 6).

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