Figure 3
Lead (Pb) suppresses critical period experience-dependent plasticity. (a) Mice were administered 50 parts per million (PPM) Pb in drinking water or water alone (control) from P8 through in vivo extracellular recordings to assess ocular dominance plasticity at P27-P29 (avg P28) (b) Laser ablation-based elemental mapping revealed dramatic Pb accumulation in visual regions including cortical layers of V1 and superior colliculus [Pb N = 1, control N = 1, both no monocular deprivation (MD)]. (c) After 3 days of MD beginning at P24-P26 (avg P25) neurons from control mice (light grey color, 6 mice, 165 cells) exhibited plasticity as quantified at the neuron-level by a shift in their responsivity from the previously deprived eye (contralateral to recording hemisphere) to the nondeprived eye, observable as a right shift in the ocular dominance score (ODS) as compared to control animals who did not receive MD (dark grey color, 3 mice, 101 cells; χ2 test of ODS distribution: χ2 = 61.3, P = 6.6 × 10−12). In contrast, V1 neurons from animals who underwent MD and were administered Pb (light teal color, 5 mice, 135 cells) did not exhibit a full ODS shift (Pb MD versus control MD: χ2 test of ODS distribution: χ2 = 17.1, P = 4 × 10−4), though some residual plasticity remained (Pb MD versus Pb no MD [dark teal color, 5 mice, 148 cells]: χ2 = 42.8, P = 4.1 × 10−8). (d) We carried out an animal-level analysis using a hierarchical linear modeling approach that takes into account within-animal variation (on average, 28.8 neurons were recorded from each mouse) wherein group (Pb or control) and experience (MD or no MD) were assigned as fixed effects and animal was assigned as a random effect to account for repeated neural measurements within each animal. The neuron level ocular dominance index (ODI) was assiged as the continuous outcome variable. After correcting for multiple comparisons using the Holm method, we confirmed plasticity was present in control mice who received MD (light grey color) as quantified by an elevated ODI compared to control animals who did not receive MD (dark grey color) (β = 0.28, Padj = 0.0002). Mice administered Pb showed significantly reduced plasticity as quantified by a reduction in ODI (Pb MD (light teal color) versus control MD (light grey color): β = −0.11, Padj = 0.04), but retained some plasticity relative to no MD animals (Pb MD (light teal color) versus Pb no MD (dark teal color): β = 0.16, Padj = 0.012). Horizontal bars indicate the least squares mean. ****P < 0.0001, ***P ≥ 0.0001 and < 0.001, **P ≥ 0.001 and < 0.01, *P ≥ 0.01 and < 0.05.
