A ventral hippocampus to nucleus accumbens pathway regulates impulsivity

Klug, M. E.; Decarie-Spain, L.; Tierno Lauer, L.; Kao, A. E.; Moody, O. P.; Morano, N. R.; Huang, H.; Arnold, D. B.; Noble, E. E.; Kanoski, S. E.

doi:10.1101/2025.11.18.689154

bioRxiv · 10.1101/2025.11.18.689154

A ventral hippocampus to nucleus accumbens pathway regulates impulsivity

Klug, M. E.·Decarie-Spain, L.·Tierno Lauer, L.·Kao, A. E.·Moody, O. P.·Morano, N. R.·Huang, H.·Arnold, D. B.·Noble, E. E.·Kanoski, S. E.

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Abstract

Heightened impulsivity is attributed with substance abuse disorders, gambling, and obesity. The ventral hippocampus (vHPC) has recently been linked with impulse control, yet the neurobiological and behavioral mechanisms through which this control occurs are unknown. A subset of vHPC neurons project to the nucleus accumbens (ACB), a brain region known for regulating reward and motivation. Here, we evaluated the role of vHPC-ACB signaling in food-directed impulsivity using fiber photometry and transsynaptic chemogenetic and behavioral approaches. Male and female rats were trained in the differential reinforcement of low rates of responding (DRL) test of impulsive action, where they learn to withhold lever presses for 20 seconds to obtain a palatable food reward. Photometry recordings during DRL revealed analogous elevations in calcium-dependent activity in the vHPC and ACB during the 5s immediately prior to a non-impulsive vs. an impulsive response. Chemogenetic silencing of ACB-projecting vHPC neurons elevated impulsive responses in DRL relative to vehicle treatment in males but not females, yet had no effect on home cage food intake, operant-based motivation to work for palatable food, impulsive choice, or anxiety-like behavior. To determine whether this impulse control circuit requires vHPC->ACB communication independent of collateral targets of ACB-projecting vHPC neurons, we utilized a novel transsynaptic viral approach to selectively silence ACB neurons that receive synaptic glutamatergic signaling from the vHPC. Results reveal that inhibition of ACB neurons receiving vHPC signaling elevates impulsive action in the DRL task relative to vehicle treatment. Collective results reveal a hippocampal-striatal circuit that regulates impulsive action in males.

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Klug, M. E., Decarie-Spain, L., Tierno Lauer, L., Kao, A. E., Moody, O. P., Morano, N. R., Huang, H., Arnold, D. B., Noble, E. E., Kanoski, S. E.. 2025-11-19. A ventral hippocampus to nucleus accumbens pathway regulates impulsivity. https://doi.org/10.1101/2025.11.18.689154

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