Change-of-mind neuroeconomic decision-making is modulated by LINC00473 in medial prefrontal cortex in a sex-dependent manner
- Romain Durand-de Cuttoli
- Orna Issler
- Samantha M. B. Pedersen
- Benjamin Yakubov
- Nusrat Jahan
- Aisha Abid
- Susanna Kasparov
- Kastalia Granizo
- Sanjana Ahmed
- Scott J. Russo
- Eric J. Nestler
- Brian M. Sweis
2025-07-11
Changing one’s mind involves reappraisals between past costs versus future value and may be altered in psychopathology. Long intergenic noncoding RNA LINC00473 in medial prefrontal cortex (mPFC) can induce stress resilience in a sex-dependent manner, but its role in cognition is unknown. We characterized decision-making behavior in male and female mice in the neuroeconomic paradigm Restaurant Row following virus-mediated expression of LINC00473 in mPFC. Mice foraged for food among varying temporal costs and subjective value while on a limited time budget. Without affecting primary deliberative decisions, LINC00473 selectively influenced re-evaluative choices in a sex-dependent manner. This included changing how mice (i) cached value with the passage of time and (ii) weighed prior mistakes, which underlie the computational bases of sensitivity to sunk costs and regret. These findings suggest that a common value function is shared between these neuroeconomic processes and reveal a bridge between molecular drivers of stress resilience and psychological mechanisms underlying sex-specific proclivities in negative rumination.