Biology subjects

Powers, R. E.

Publications and source records attributed to Powers, R. E..

4 recordsLinked to original sources

bioRxiv2026

Distinct ensembles in the prelimbic cortex track different measures of motivation for cocaine and water reinforcers.

The motivation to pursue drugs is a fundamental element of substance use. Different tasks assess motivation in the face of effort, punishment, or the absence of the drug, and recent studies have suggested that a shared latent variable may drive behavior across these tasks. The prelimbic cortex (PL) is implicated in these behaviors, but it is unknown if its role is driven by shared or distinct neural ensembles. We recorded PL activity using in vivo endoscopic calcium imaging in 32 male and female Sprague-Dawley rats as they completed cocaine or water self-administration, extinction, progressive ratio, and punished self-administration. We found that behavior across tasks was driven by a single latent variable in water, but not cocaine rats. We also found distinct neural populations that tracked reward pursuit. We found that one population of cost-sensitive neurons had significantly fewer neurons present during the progressive ratio task. A second population of reward-sensitive neurons had significantly fewer neurons present during the extinction task. Individual rats with more of these neurons present during the task had significantly higher levels of reward pursuit in the progressive ratio and extinction tasks, respectively. Furthermore, this relationship was true across cocaine and water rats, suggesting a general role in motivation independent of reward type. When we examined whether shared patterns of neural activity predicted shared patterns of behavior across the tasks, we found no relationships. Thus, our findings suggest that distinct facets of reward motivation are tracked by distinct ensembles in the PL, rather than a shared ensemble.

neuroscience↗

bioRxiv2025

A shared ensemble in the prelimbic cortex links impulsivity and anxiety-like behavior.

Mental health disorders often share overlapping behavioral and neural features, yet it remains unclear why these relationships emerge or whether they reflect common underlying neural processes. To explore this, we recorded prelimbic (PL) activity using endoscopic calcium imaging as rats completed a battery of tasks assessing impulsivity, distress tolerance, anxiety-like behavior, incentive salience (Pavlovian conditioned approach), and sensation-seeking in a novel environment (locomotor activity). By collecting neural and behavioral measures across all tasks within each animal, we were able to investigate whether PL activity tracked processes that were either unique to individual behaviors, shared across multiple behaviors, or both. We found that PL activity was significantly predictive of each of the behaviors except locomotor activity. Subsequent analyses revealed shared behavioral structure across tasks, with one latent dimension reflecting high impulsivity and low anxiety-like behavior. Individual variability across this particular dimension was strongly predicted by a neural structure comprising shared PL activity across four of the behaviors. Furthermore, this relationship was driven by a subset of PL neurons that shared patterns of activity across multiple tasks, forming a shared neural ensemble. Importantly, animals with a greater tendency to share neural ensembles exhibited a stronger link between high impulsivity and low anxiety-like behavior. These findings suggest that a small, shared ensemble of PL neurons tracked activity across multiple clinically-relevant behaviors to predict an approach/avoidance phenotype characterized by high impulsivity and low anxiety. This points toward a targetable neural population that may help explain why diverse psychiatric symptoms often co-occur within individuals.

neuroscience↗

bioRxiv2024

Prelimbic Cortex Activity Predicts Anxiety-Like Behavior in the Elevated Plus Maze

The medial prefrontal cortex (mPFC) plays a critical role in emotional regulation, and its dysregulation is linked to anxiety disorders. In particular, the prelimbic cortex (PrL) of the mPFC is thought to modulate anxiety-related behaviors, though its precise role remains debated. Here, we used endoscopic in vivo calcium imaging to assess PrL neuronal activity in male and female Sprague-Dawley rats performing in the Elevated Plus Maze (EPM), a widely used task to measure anxiety-like behavior. We found that animals that spent less time in the open arms exhibited higher PrL activity in the open arms, suggesting that heightened PrL activity may reflect greater anxiety or increased avoidance behavior. These results suggest that the PrL may play a role in regulating the emotional response to anxiety-provoking situations, potentially influencing the tolerance for exposure to threatening environments.

neuroscience↗

bioRxiv2024

Distinct populations suppress or escalate intake of cocaine paired with aversive quinine.

BackgroundOnly a subset of individuals who encounter drugs of abuse become habitual users. Aversive subjective effects like coughing and unpleasant taste are predictors for continued use. While several preclinical studies have explored self-administration involving aversive cues, none have simultaneously introduced aversion with the initial drug self-administration. We aimed to develop a clinically relevant model by pairing intravenous cocaine with intraoral quinine self-administration from the outset and investigating whether repeated exposure to an aversive stimulus would alter its hedonic value under laboratory conditions. MethodsTwenty-seven male and female Sprague Dawley rats self-administered intravenous/intraoral (cocaine/quinine) for 2 hr/day over 14 days. This was followed by a 1-day quinine-only extinction session, a 3-day return to self-administration, and an intraoral infusion session to assess quinine taste reactivity (TR). ResultsWe identified three distinct groups. The first self-administered very little cocaine, while the second sharply escalated cocaine intake. Both groups had similar aversive TR to quinine, suggesting that the escalating group did not habituate to the aversive cue but pursued drug despite it. We also identified a third group with high initial intake that decreased over time. This decrease predicted high aversive TR, and we argue this group may represent individuals who "overindulge" on their first use and subsequently find self-administration to be aversive. ConclusionsOur novel model mimics real-world variability in initial interactions with drugs of abuse and yields three distinct groups that differ in self-administration patterns and aversive cue valuation.

animal behavior and cognition↗