A ventral hippocampus to nucleus accumbens pathway regulates impulsivity in male but not female rats

Heightened impulsivity is associated 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 occurs are unknown. A subset of vHPC neurons projects to the nucleus accumbens shell (ACBsh), a brain region known for regulating reward and motivation. Here, we evaluated the role of vHPC-ACBsh 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 s to obtain a palatable food reward. Photometry recordings during DRL revealed elevations in calcium-dependent activity in the vHPC during the 5 s immediately prior to a non-impulsive vs. an impulsive response in males but not females. Chemogenetic silencing of ACBsh-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->ACBsh communication independent of collateral targets of ACBsh-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 ACBsh neurons receiving vHPC signaling elevates impulsive action in the DRL task relative to vehicle treatment. Collective results reveal a sex-specific hippocampal-striatal circuit that regulates impulsivity.