Biology subjects

Vento, P. J.

Publications and source records attributed to Vento, P. J..

2 recordsLinked to original sources

bioRxiv2025

Long-lasting Avoidance Induced by Repeated Stimulation of the Rostromedial Tegmental Nucleus

Adaptive decision-making requires the ability to weigh the relative costs versus the benefits of our actions and to flexibly respond to changing environmental contingencies. While midbrain dopamine (DA) has been a major focus of study for its role in associative learning, motivation, and reward seeking, far less is known regarding the contribution of inhibitory dopamine inputs in promoting behavioral inhibition and avoidance learning. The rostromedial tegmental nucleus (RMTg) sends dense GABAergic projections to DA neurons in the ventral tegmental area (VTA) and mounting evidence suggests the RMTg-VTA circuit is required to suppress reward seeking under punishment, but it remains unclear whether stimulation of this pathway is sufficient to drive learning and promote shifts in cost-benefit decisions. To test this, we developed two separate tasks of passive and active avoidance in rats where lever pressing for food reward was associated with repeated contingent optogenetic stimulation of the RMTg-VTA pathway. In a one-lever fixed ratio 5 food-seeking task, we found that pairing RMTg-VTA stimulation with reward delivery caused a robust, yet transient suppression of reward seeking that quickly returned to baseline after contingent stimulation ceased. When given an alternative reward choice, however, RMTg-VTA stimulation caused a rapid and enduring shift in subjective choice leading to persistent and selective avoidance of the stimulation-paired reward. These findings support a multifaceted role for the RMTg-VTA pathway in learning and decision-making and provide key insights into the neural mechanisms underlying behavioral avoidance and maladaptive reward seeking.

neuroscience↗

bioRxiv2023

Pumping the brakes: Rostromedial tegmental inhibition of compulsive cocaine seeking

Addiction is marked by aberrant decision-making and an inability to suppress inappropriate and often dangerous behaviors. We previously demonstrated that inactivation of the rostromedial tegmental nucleus (RMTg) in rats causes persistent food seeking despite impending aversive footshock, an effect strikingly similar to the punishment resistance observed in people with a history of protracted drug use [1]. Here, we extend these studies to demonstrate chemogenetic silencing of RMTg axonal projections to the ventral tegmental area (VTA) (RMTg{lozenge}VTA pathway) causes rats to endure significantly more footshock to receive cocaine infusions. To further test whether activation of this circuit is sufficient to suppress reward seeking in the absence of an overtly aversive stimulus, we used temporally specific optogenetic stimulation of the RMTg{lozenge}VTA pathway as a "punisher" in place of footshock following lever pressing for either food or cocaine reward. While optical stimulation of the RMTg{lozenge}VTA pathway robustly suppressed lever pressing for food, we found that stimulation of this circuit had only modest effects on suppressing responding for cocaine infusions. Even though optical RMTg{lozenge}VTA stimulation was not particularly effective at reducing ongoing cocaine use, this experience nevertheless had long-lasting consequences, as reinstatement of drug seeking in response to cocaine-associated cues was profoundly suppressed when tested nearly two weeks later. These results suggest the RMTg may serve as a useful target for producing enduring reductions in drug craving, particularly during periods of abstinence from drug use.

neuroscience↗