Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.26.062950v1?rss=1 Authors: Wilson, C. A., Fouda, S., Sakata, S. Abstract: Neuronal activity can modify Alzheimer's disease pathology. Although overexcitation of neurons can facilitate disease progression, the induction of cortical gamma oscillations can reduce amyloid load and improve cognitive functions in mouse models. These beneficial effects of gamma oscillations can be caused by either optogenetic activation of cortical parvalbumin-positive (PV+) neurons or 40 Hz repetitive sensory stimuli. However, given the fact that cortical gamma oscillations can be induced by multiple mechanisms, it is still unclear whether other approaches to induce gamma oscillations can also be beneficial. Here we show that optogenetic activation of PV+ neurons in the basal forebrain (BF) increases amyloid burden, rather than reducing it. We applied 40 Hz optical stimulation in the BF of 5xFAD mice by expressing channelrhodopsin-2 (ChR2) in PV+ neurons. After one-hour induction of cortical gamma oscillations over three days, we observed the increase in the concentration of amyloid-{beta}42 in the frontal cortical region, but not amyloid-{beta}40. The density of amyloid plaques also increased in the medial prefrontal cortex and the septal nuclei, both of which are targets of BF PV+ neurons. These results suggest that effects of cortical gamma oscillations on Alzheimer's disease pathology can be bidirectional depending on their induction mechanisms. Copy rights belong to original authors. Visit the link for more info