In vivo quantification of Arc::dVenus reporter in the visual cortex of rTg4510 mice. (a) Experiment outline. Structural visual stimulation paradigm described previously in  was followed by cranial window implantation over the medial extrastriate visual cortex and imaging on a multiphoton microscope. After the imaging, the brains were collected and processed for immunohistochemical analysis. (b) Sample maximum intensity projections of in vivo-acquired multiphoton z-stacks from the layer II/III of the medial extrastriate visual cortex, showing Arc::dVenus reporter (shown in green) expression induced by the visual stimulation. Scale bar = 100 μm. (c) Frequency distribution histograms of activity-induced Arc::dVenus fluorescence in individual visual cortex neurons of rTg4510 mice (n = 8 mice, 2212 neurons) and control littermates (n = 5 mice, 1043 neurons). AU, arbitrary units. n.s., not significant, P = 0.27. (d) Sample single-section in vivo multichannel micrographs of the same visual cortex site from an rTg4510 mouse before (left) and after (right) the intravenous delivery of a tangle-binding dye methoxy-X04 (red). Fluorescent angiogram (blue) was used as a landmark pattern during the image analysis. Arrowheads points to a dVenus-positive neuron with an NFT and the inset shows a close-up view of this neuron. Scale bar = 100 μm. Inset size = 20 × 20 μm. (e) Frequency distribution histograms of activity-induced Arc::dVenus fluorescence in rTg4510 neurons without tangles (n = 4 mice, 720 neurons) and with tangles (n = 4 mice, 101 neurons). AU, arbitrary units. n.s., not significant, P = 0.083.