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. 2023 Apr 21;21(4):e3002096.
doi: 10.1371/journal.pbio.3002096. eCollection 2023 Apr.

Monocular deprivation during the critical period alters neuronal tuning and the composition of visual circuitry

Thomas C Brown  1 , Aaron W McGee  1
Affiliations

Monocular deprivation during the critical period alters neuronal tuning and the composition of visual circuitry

Thomas C Brown et al. PLoS Biol. .

Abstract

Abnormal visual experience during a developmental critical period degrades cortical responsiveness. Yet how experience-dependent plasticity alters the response properties of individual neurons and composition of visual circuitry is unclear. Here, we measured with calcium imaging in alert mice how monocular deprivation (MD) during the developmental critical period affects tuning for binocularity, orientation, and spatial frequency for neurons in primary visual cortex. MD of the contralateral eye did not uniformly shift ocular dominance (OD) of neurons towards the fellow ipsilateral eye but reduced the number of monocular contralateral neurons and increased the number of monocular ipsilateral neurons. MD also impaired matching of preferred orientation for binocular neurons and reduced the percentage of neurons responsive at most spatial frequencies for the deprived contralateral eye. Tracking the tuning properties for several hundred neurons before and after MD revealed that the shift in OD is complex and dynamic, with many previously monocular neurons becoming binocular and binocular neurons becoming monocular. Binocular neurons that became monocular were more likely to lose responsiveness to the deprived contralateral eye if they were better matched for orientation prior to deprivation. In addition, the composition of visual circuitry changed as population of neurons more responsive to the deprived eye were exchanged for neurons with tuning properties more similar to the network of responsive neurons altered by MD. Thus, plasticity during the critical period adapts to recent experience by both altering the tuning of responsive neurons and recruiting neurons with matching tuning properties.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Measuring OD plasticity with calcium imaging at cellular resolution.
(A) Imaging fields for P28 (left) and P32 after 4 days of MD of the contralateral eye (right). Neurons are color-coded to their ODI score. 1 corresponds to monocular contralateral neurons. −1 corresponds to monocular ipsilateral neurons. (B) Average neuronal ODI scores for nondeprived P28–P32 mice (mean ODI = 0.43, n = 8 mice), P32 mice (mean ODI .57, n = 5 mice), and P32 mice after 4 days of MD (mean ODI = −0.09, n = 7 mice). P32 mice after 4 days of MD possess significantly different ODI values than both P28 and P32 nondeprived mice. (1-way ANOVA) (C) Sum ODI scores for the same mice as in panel B. P28 (mean ODI = 0.39, n = 8 mice), P32 (mean ODI = 0.61, n = 5 mice), and P32MD (mean ODI = −0.02, n = 7 mice). P32 mice after 4 days of MD possess significantly different ODI values than both P28 and P32 nondeprived mice. (1-way ANOVA). (D) Histogram of ODI scores for nondeprived P28 (left), nondeprived P32 mice (middle), and P32 mice following 4 days (4d) of MD (right) from panel B. (E, F) Mean normalized fluorescence (delta F over F, dF/F) values for neurons responding to the contralateral eye (C) and ipsilateral eye (I) for each nondeprived mouse (P28–P32, n = 13) and mice after 4 days of MD (P32 4d MD, n = 7) (Welch’s t test). (G) Cumulative histogram of the distribution of normalized fluorescence responses (dF/F) from P28–P32 mice for visual stimuli provided to the contralateral eye (C, n = 1,566 neurons) or the ipsilateral eye (I, n = 766 neurons), as well as P32 mice after 4 days of MD of the contralateral eye (C, n = 447 neurons; I, n = 579 neurons). https://data.mendeley.com/datasets/3yt5kpzw6d. MD, monocular deprivation; OD, ocular dominance; ODI, ocular dominance index; P, postnatal day.
Fig 2
Fig 2. MD during the critical period reduces binocular orientation matching and the number of responding neurons across most spatial frequencies.
(A) Examples of heat maps for responses of the contralateral eye (top) and ipsilateral eye (bottom) across orientation and SF for binocular neurons with a difference of orientation preference of 5 degrees (left), 16 degrees (middle), and 40 degrees (right) from a naïve mouse (left) and mice after 4 days of MD (middle, right). (B) Cumulative distribution of difference in preferred orientation for the 2 eyes by binocular neurons for nondeprived mice (n = 474, median = 20 degrees) and after 4 days of MD of the contralateral eye (n = 162, median = 26 degrees) (P = 0.018; Kolmogorov–Smirnov test of cumulative distribution (KS test)). (C) The mean preferred SF for neurons responding to the contralateral eye (C) and ipsilateral eye (I) for each nondeprived mouse (P28–P32, n = 13) and mice after 4 days of MD (P32MD, n = 7). The distribution and median for the population of neurons are presented as violin plots with the median indicated by a horizontal bar (P28–P32, C = 1,566 neurons, I = 766 neurons; P32MD, C = 447 neurons, I = 579 neurons). There is no statistical difference in the mean preferred SF for the C and I eye per mouse for either nondeprived mice or following 4 days of MD (paired t test). (D) The percent of visually responsive neurons per mouse that displayed a significant response to each SF at any orientation (2-way ANOVA with Sidak’s multiple comparison test for 8 comparisons). https://data.mendeley.com/datasets/3yt5kpzw6d. MD, monocular deprivation; SF, spatial frequency.
Fig 3
Fig 3. Tracking neurons longitudinally reveals an exchange of monocular and binocular neurons as well as neurons active in visual circuitry during OD plasticity.
(A) Histogram of ODI values at P28 (left) and at P32 after 4 days of MD of the contralateral eye (right) for visually responsive neurons, nonresponsive (NR) neurons at P28 that were visually responsive at P32, and visually responsive neurons that became nonresponsive (NR) at P32, for 6 mice receiving 4 days of MD starting at P28. A line between the 2 histograms connects points that indicate the mean ODI of the population of visually responsive neurons at P28 and P32MD, respectively. (B) Sankey diagram of the stability and interconversion between P28 and P32MD for neurons that were nonresponsive (NR, grey), monocular contralateral (C, red), binocular (B, green) and monocular ipsilateral (I, blue) for the neurons presented in panels A. (C) The mean ODI for all neurons by category presented in panels A and D. The mean ODI of neurons that were visually responsive at P28 (black) and the mean of ODI at P32 of these neurons categorized as monocular contralateral (red), binocular (green), and monocular ipsilateral (blue) at P28. The black horizonal line indicates the mean ODI of all neurons visually responsive at P32 that were also visually responsive at P28. In addition, the mean ODI of neurons at P28, which were nonresponsive (NR) at P32, and the mean ODI of neurons at P32, which were nonresponsive at P28, are plotted to the right. https://data.mendeley.com/datasets/3yt5kpzw6d. MD, monocular deprivation; OD, ocular dominance; ODI, ocular dominance index; NR, nonresponsive.
Fig 4
Fig 4. MD during the critical period degrades binocular orientation matching.
(A) Cumulative distribution of difference in preferred orientation for the 2 eyes by neurons that were binocular (B—B) both at P28 (n = 102, median = 19 degrees) and at P32 after 4 days of MD (n = 102, median = 34 degrees). (P < 0.0001; KS test). (B) Cumulative distribution of difference in preferred orientation for neurons that were either contralateral monocular (C) or ipsilateral monocular (I) at P28 and binocular (B) at P32 following MD (C-B, n = 87, median 39 degrees; I-B, n = 36, 30 degrees) (C) Cumulative distribution of difference in preferred orientation for neurons that were binocular at P28 but nonresponsive at P32 (B-NR, n = 33, median = 19 degrees) and at P32 after 4 days of MD (NR-B, n = 102, median = 34 degrees). (P < 0.0001; KS test). (D) Cumulative distribution of difference in preferred orientation for the 2 eyes by all binocular neurons (All) at P28 (n = 243, median = 19 degrees) and P32 after 4 days of MD (n = 246, median = 34 degrees). (P < 0.0001; KS test). (E) The cumulative distribution of difference in preferred orientation (degrees) for neurons that were binocular at P28 but either lost responsiveness to the fellow ipsilateral eye to become contralateral monocular (B-C, red, n = 46 neurons; median 29 degrees) or lost responsiveness to the deprived contralateral eye to become ipsilateral monocular (B-I, blue, n = 62 neurons; median 15 degrees). These distributions are statistically different (P = 0.02, KS test). https://data.mendeley.com/datasets/3yt5kpzw6d. MD, monocular deprivation.
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