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[Preprint]. 2025 Jul 18:2025.07.15.664949. [Version 1] doi: 10.1101/2025.07.15.664949

Optogenetic inhibition reveals distinct contributions of medial prefrontal cortex to intertemporal choice in young and aged rats

Mojdeh Faraji, Caesar M Hernandez, Alexa-Rae Wheeler, Todd J Sahagian, Scott W Harden, Charles J Frazier, Matthew R Burns, Barry Setlow, Jennifer L Bizon
PMCID: PMC12338721  PMID: 40791560

Abstract

The ability to choose adaptively between rewards differing in magnitude and delay (intertemporal choice) is critical for numerous life outcomes. Compared to younger adults, older adults tend to exhibit greater preference for large, delayed over small, immediate rewards (i.e., less delay discounting), which could lead to missed opportunities to obtain resources necessary for quality of life. Intertemporal choice is mediated by the prefrontal cortex, but how this is impacted by advanced age is not well understood. We used optogenetic inactivation to investigate contributions of medial prefrontal cortex (mPFC) during distinct components of an intertemporal choice task in young and aged rats. mPFC inactivation during deliberation (during decisions between small, immediate vs. large, delayed rewards) increased preference for large, delayed rewards in both age groups. In contrast, inactivation during delays prior to large reward delivery increased preference for large, delayed rewards only in aged rats. Choices were unaffected by inactivation during other task phases. Results suggest that mPFC integrates information regarding anticipated outcomes into the decision process across the whole lifespan, but that only in aging is mPFC critical for consolidating information regarding reward delays into the decision structure in order to modulate choice behavior.

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