Brown, S. O. | Search bioRxiv

bioRxiv2026

Cholinergic interneurons in the nucleus accumbens regulate the initiation of natural reward approach

Despite their established role in motivated behavior, how nucleus accumbens (NAc) cholinergic interneurons (CINs) contribute to natural reward seeking remains unclear. Here, we report that NAc CINs are key modulators of the approach phase of reward pursuit. Using in vivo fiber photometry in Chat-ires-Cre mice, we show that NAc CINs are robustly activated during the approach towards several salient stimuli including food, a social target, and a familiar object. We also provide evidence that this activation is potentially driven by olfactory cues. Disrupting NAc CIN function via targeted expression of a membrane-tethered toxin results in a delayed approach towards both food and a social target, but no alterations in object investigation, general locomotion or anxiety-related measures. Together, these findings identify NAc CINs as regulators of the initiation of natural reward approach and suggest that they link sensory information with onset of motivated action.

neuroscience↗

bioRxiv2024

Diabetes alters neuroeconomically dissociable forms of mental accounting

Those with diabetes mellitus are at high-risk of developing psychiatric disorders, yet the link between hyperglycemia and alterations in motivated behavior has not been explored in detail. We characterized value-based decision-making behavior of a streptozocin-induced diabetic mouse model on a naturalistic neuroeconomic foraging paradigm called Restaurant Row. Mice made self-paced choices while on a limited time-budget accepting or rejecting reward offers as a function of cost (delays cued by tone-pitch) and subjective value (flavors), tested daily in a closed-economy system across months. We found streptozocin-treated mice disproportionately undervalued less-preferred flavors and inverted their meal-consumption patterns shifted toward a more costly strategy that overprioritized high-value rewards. We discovered these foraging behaviors were driven by impairments in multiple decision-making systems, including the ability to deliberate when engaged in conflict and cache the value of the passage of time in the form of sunk costs. Surprisingly, diabetes-induced changes in behavior depended not only on the type of choice being made but also the salience of reward-scarcity in the environment. These findings suggest complex relationships between glycemic regulation and dissociable valuation algorithms underlying unique cognitive heuristics and sensitivity to opportunity costs can disrupt fundamentally distinct computational processes and could give rise to psychiatric vulnerabilities.

neuroscience↗