Biology subjects

Gyawali, U.

Publications and source records attributed to Gyawali, U..

3 recordsLinked to original sources

bioRxiv2025

Reducing astrocyte calcium in the nucleus accumbens core increases reward valuation

Astrocyte dysfunction within the nucleus accumbens (NAc) has been increasingly implicated in maladaptive reward processing and the development of addiction-like behaviors. In this study, we investigated how impairing astrocyte calcium signaling in the NAc core influences consummatory reward behaviors and reward valuation. Using a viral approach to express the human plasma membrane calcium ATPase (hPMCA) in NAc core astrocytes in male rats, we selectively reduced intracellular astrocyte calcium dynamics. Blunting astrocyte calcium signaling led to increased self-administration of both sucrose and cocaine on a low effort fixed-ratio schedule of reinforcement. Behavioral economic analysis revealed enhanced reward motivation and valuation in hPMCA-expressing rats as compared to controls. Notably, reduction of astrocyte calcium signaling did not alter cocaine-induced locomotor sensitization, indicating a dissociation between astrocytic regulation of reward valuation and other cocaine-related behaviors. Collectively, these results identify astrocyte calcium dynamics in the NAc core as a key constraint on motivational drive and reward valuation.

neuroscience↗

bioRxiv2022

Dopamine in the Dorsal Bed Nucleus of Stria Terminalis signals Pavlovian sign-tracking and reward violations

Midbrain and striatal dopamine signals have been extremely well characterized over the past several decades, yet novel dopamine signals and functions in reward learning and motivation continue to emerge. A similar characterization of real-time sub-second dopamine signals in areas outside of the striatum has been limited. Recent advances in fluorescent sensor technology and fiber photometry permit measurement of dopamine binding correlates, which can divulge basic functions of dopamine signaling in non-striatal dopamine terminal regions, like the dorsal bed nucleus of the stria terminalis (dBNST). Here, we record GRABDA signals in the dBNST during a Pavlovian lever autoshaping task. We observe greater Pavlovian cue-evoked dBNST GRABDA signals in sign-tracking (ST) compared to goal-tracking/intermediate (GT/INT) rats and the magnitude of cue-evoked dBNST GRABDA signals decrease immediately following reinforcer-specific satiety. When we deliver unexpected reward or omit expected reward, we find that dBNST dopamine signals encode bidirectional reward prediction errors in GT/INT rats, but only positive prediction errors in ST rats. Since sign- and goal-tracking approach strategies are associated with distinct drug relapse vulnerabilities, we examined the effects of experimenter-administered fentanyl on dBNST dopamine associative encoding. Systemic fentanyl injections do not disrupt dBNST cue discrimination but generally potentiate dBNST dopamine signals. These results reveal multiple dBNST dopamine correlates of learning and motivation that depend on the Pavlovian approach strategy employed.

neuroscience↗

bioRxiv2020

Basolateral amygdala to nucleus accumbens projections differentially mediate flexibility of sign- and goal-tracking rats

Rats rely on communication between basolateral amygdala (BLA) and nucleus accumbens (NAc) to express lever directed approach in a Pavlovian lever autoshaping (PLA) task that distinguishes sign- and goal-tracking rats. While sign-tracking rats inflexibly respond to cues even after the associated outcome is devalued, goal-tracking rats flexibly suppress conditioned responding during outcome devaluation. Here, we sought to determine whether BLA-NAc communication in sign-trackers drives rigid appetitive approach that is insensitive to manipulations of outcome value. Using a contralateral chemogenetic inactivation design, we injected contralateral BLA and NAc core with inhibitory DREADD (hm4D-mcherry) or control (mcherry) constructs. To determine sign- and goal-tracking groups, we trained rats in five PLA sessions in which brief lever insertion predicts food pellet delivery. We sated rats on training pellets (devalued condition) or chow (valued condition) prior to systemic clozapine injections (0.1 mg/kg) to inactivate BLA and contralateral NAc during two outcome devaluation probe tests, in which we measured lever and foodcup approach. Contralateral BLA-NAc chemogenetic inactivation promoted flexible lever approach in sign-tracking rats, but disrupted flexible food-cup approach in goal-tracking rats. Consistent with a prior BLA-NAc disconnection lesion study, we find contralateral chemogenetic inactivation of BLA and NAc core reduces lever, but not foodcup approach in PLA. Together these findings suggest rigid appetitive associative encoding in BLA-NAc of sign-tracking rats hinders the expression of flexible behavior when outcome value changes.

neuroscience↗