Effects of optogenetic stimulation of basal forebrain parvalbumin neurons on Alzheimer's disease pathology

Caroline A. Wilson, Sarah Fouda, Shuzo Sakata

Research output: Contribution to journalArticle

Abstract

Neuronal activity can modify Alzheimer's disease pathology. Overexcitation of neurons can facilitate disease progression whereas the induction of cortical gamma oscillations can reduce amyloid load and improve cognitive functions in mouse models. Although previous studies have induced cortical gamma oscillations by either optogenetic activation of cortical parvalbumin-positive (PV+) neurons or sensory stimuli, 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 by expressing channelrhodopsin-2 (ChR2) in PV+ neurons of 5xFAD mice. After one-hour induction of cortical gamma oscillations over three days, we observed the increase in the concentration of amyloid-β42 in the frontal cortical region, but not amyloid-β40. Amyloid plaques were accumulated more in the medial prefrontal cortex and the septal nuclei, both of which are targets of BF PV+ neurons. These results suggest that beneficial effects of cortical gamma oscillations on Alzheimer's disease pathology can depend on the induction mechanisms of cortical gamma oscillations.
Original languageEnglish
Article number15456
Number of pages21
JournalScientific Reports
Volume10
Issue number1
DOIs
Publication statusPublished - 22 Sep 2020

Keywords

  • deep brain stimulation
  • amyloid beta
  • gamma oscillations
  • optogenetics
  • Alzheimer's disease

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