Abstract
Grape-derived polyphenols have been investigated for their role in promoting memory in model systems of stress, but little is known about select subpopulations of neurons that are influenced by polyphenols to improve memory performance. Granule neurons in the hippocampal dentate gyrus are vulnerable to stressors that impair contextual memory function and can be influenced by dietary polyphenols. We utilized a c-fos-tTA/TRE-ChR2 optogenetics model in which neurons activated during fear learning are labeled with ChR2-mCherry and can be optically reactivated in a different context to recapitulate the behavioral output of a related memory. Treatment with dietary polyphenols increased fear memory recall and ChR2-mCherry expression in dentate gyrus neurons, suggesting that dietary polyphenols promote recruitment of neurons to a fear memory engram. We show that dietary polyphenols promote memory function and offer a general method to map cellular subpopulations influenced by dietary polyphenols, in part through the mechanism of c-Fos expression enhancement.
Highlights
Grape-derived polyphenols have been investigated for their role in promoting memory in model systems of stress, but little is known about select subpopulations of neurons that are influenced by polyphenols to improve memory performance
To confirm the inducible and activity-dependent expression of ChR2-mCherry in the contextual fear conditioning (CFC) paradigm, we examined its expression at different time points of testing
We have shown through an optogenetics model that dietary polyphenols in the form of bioactive dietary polyphenol preparation (BDPP) promote recruitment of dentate gyrus (DG) granule neurons to fear memory through enhanced expression of c-Fos, as reflected by increased labeling of recently activated neuronal subpopulations with ChR2-mCherry (Fig. 4)
Summary
Grape-derived polyphenols have been investigated for their role in promoting memory in model systems of stress, but little is known about select subpopulations of neurons that are influenced by polyphenols to improve memory performance. We show that BDPP treatment in c-fos-tTA/TRE-ChR2mCherry mice results in increased c-fos-promoter-induced expression of ChR2-mCherry and endogenous c-Fos, as well as increased recapitulation of fear memory upon optical stimulation in a distinct context.
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