Fig. 3: Age modifies the synaptic plasticity response to overstimulation.
From: Age-related dysregulation of homeostatic control in neuronal microcircuits
a–c, E:I ratio (Welch’s t-test, Con versus Stim, 3 months: P = 0.022; MWRST, 8 months: P = 0.795; MWRST, 12 months: P = 0.038) (a), mIPSP frequency (Hz) (t-test, Con versus Stim, 3 months: P = 0.030; MWRST, 8 months: P = 0.959; t-test, 12 months:, P < 0.001) (b) and mEPSP amplitude (mV) (MWRST, Con versus Stim, 3 months: P < 0.001; MWRST, 8 months: P < 0.001; MWRST, 12 months: P < 0.001) (c) for overstimulated mice at 3 (orange), 8 (green) and 12 (gray) months after 3 d of overstimulation versus age-matched controls (black). d, Images showing a c-Fos-positive V1 L2/3 neuron (left, green), VGAT puncta (middle, red) and a merged image (right) of mice expressing AAV1-C-FOS-eYFP. Scale bar, 5 µm. e, Density of VGAT puncta at c-Fos-positive neurons for overstimulated mice at 3 (orange), 8 (green) and 12 (gray) months normalized to age-matched controls (black) (MWRST, Con versus Stim, 3 months: P < 0.001; MWRST, 8 months: P = 0.497; t-test, 12 months: P = 0.043). f, Spine size from c-Fos-positive dendrites in overstimulated mice at 3 (orange), 8 (green) and 12 (gray) months normalized to age-matched controls (black) (t-test, Con versus Stim, 3 months: P = 0.032; t-test, 8 months: P = 0.495; t-test, 12 months: P = 0.015). g, Example of c-Fos-positive neurons in V1 (top), and colocalization of VGAT puncta with c-Fos-positive dendrite (bottom). Scale bars, 10 µm (top) and 2 µm (bottom). h, Correlation between dendritic structural E:I ratio and c-Fos intensity per dendrite across stimulated age groups; each point represents an animal average ± s.e.m. (3 months, orange; 8 months, green; 12 months, gray; Pearson correlation, E:I ratio versus c-Fos intensity, r = 0.70, P = 0.025). i, Schematic showing overstimulation results in lower c-Fos levels (green), reduced spine size and increased VGAT (red dots) density in 3-month-old animals, while in 12-month-old animals overstimulation drove higher c-Fos levels, larger spines and decreased VGAT density. Data were obtained from 54 animals for a–c, 18 animals for e and f and 10 animals for h. *P < 0.05, **P < 0.01, ***P < 0.001. Two-sided tests were used throughout. Detailed statistics are reported in Supplementary Table 3. Cumulative distributions and comparisons for overstimulated groups and age-matched controls for c, e and f are shown in Supplementary Fig. 3. Data are presented as the mean ± s.e.m., with individual data points (gray dots), or as a cumulative distribution.
