Figure 2

Increased post-light and spontaneous LFPs generated during the optogenetic pulse train is correlated with progressive AD occurrence. (a,b) Magnification of intra-train local field recordings from the 40th stimulation of two animals with progressive (a) and non-progressive (b) ADs. Blue traces: light pulses. Green traces: detected LFP events, categorized as induced (i-LFP) or spontaneous (s-LFP), while directly light-evoked LFPs, coinciding with the light pulse (L), were not included in analysis (see Results). (c,d) The number of i-LFPs and s-LFPs per light pulse was increased in the Progr AD group compared to the Non-Progr AD group (unpaired t-tests), especially s-LFPs. (e) In CaMKII-ChR2 mice with progressive light-induced ADs (n = 11, see Fig. 4), the amount of s-LFPs generated per light pulse was not different from the Thy1-ChR2 Progr group (n = 4, unpaired t-test). Thus groups were pooled for further analysis. (f,g) Aligning data by the stimulation producing the first progressive ipsilateral AD (see Results), a 20% increase in s-LFPs (f, repeated measures ANOVA with Dunnett’s post-hoc test) coincides in time with the start of progressive AD generation (g, Friedman test with Dunn’s post-hoc test). Binned data, three stimulations per bin; PreAD: consecutive bins preceding the first progressive AD; AD: consecutive bins from the first progressive AD. Asterisks: significance in post-hoc tests. (h) Boxplots of s-LFP characteristics for the pooled progressive AD group (1115 data points from 15 animals). Line: median, box: 25–75th percentile, bars: min/max. Scale bars: (a & b) 3 mV, 50 ms. Error bars: ±SD, except (h). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, ns: non-significant; see Results for exact P-values.