Biology subjects

Ostlund, S. B.

Publications and source records attributed to Ostlund, S. B..

7 recordsLinked to original sources

bioRxiv2026

The Dorsomedial Prefrontal Cortex Uses Reward Predictions to Regulate How Rewards Are Pursued

Reward-predictive cues regulate not only whether but how rewards are pursued, and their influence depends on the strength of their predictive relationship with reward. Whereas weak cues signaling sparse or uncertain reward invigorate instrumental reward seeking, cues signaling imminent reward produce little net invigoration of instrumental behavior and instead promote conditioned goal-approach. We propose that this reflects two opposing influences: an automatic motivational impulse to seek reward, and a top-down, expectancy-dependent control process that constrains it. On this view, the muted or even suppressive effect of imminent-reward cues on instrumental reward seeking reflects an active constraint on motivation rather than its absence. Consistent with this account, we found that selectively devaluing the predicted reward unmasked a latent motivational influence. Cues for imminent reward now invigorated rather than constrained instrumental seeking, suggesting the involvement of a goal-directed regulatory process. Separately, shifting rats from hunger to general satiety abolished the cue-specific regulation of instrumental seeking. We then tested whether the dorsomedial prefrontal cortex (dmPFC) mediates this control. Bulk calcium recordings revealed phasic dmPFC activity that encoded predicted reward probability, dipped when reward was omitted, and covaried with instrumental performance in a cue-dependent manner. Moreover, chemogenetic dmPFC inhibition disrupted the cue-specific regulation of instrumental seeking, leaving rats unable to use these predictions to determine how vigorously to press. These findings identify the dmPFC as a substrate for top-down, expectancy-dependent control over reward pursuit and suggest that its dysfunction may contribute to impulsive or maladaptive reward seeking.

neuroscience↗

bioRxiv2025

Dopamine supports reward prediction to constrain reward seeking

Reward predictions not only promote reward pursuit, they also shape how reward is pursed. Such predictions are supported by environmental cues that signal reward availability and probability. Such cues trigger dopamine release in the nucleus accumbens core (NAc). Thus, here we used dopamine sensor fiber photometry, cell-type and pathway-specific optogenetic inhibition, Pavlovian cue-reward conditioning, and test of cue-induced reward-pursuit strategy in male and female rats, to ask whether cue-evoked phasic dopamine release is shaped by reward prediction to support reward pursuit. We found that cue-evoked NAc core dopamine is positively shaped by reward prediction and inversely relates to and predicts instrumental reward seeking. Cues that predicted imminent reward with high probability triggered a large NAc dopamine response and this was associated checking for the expected reward in the delivery location, rather than instrumental reward seeking. Cues that predicted reward with low probability elicited less dopamine and this was associated with a bias towards seeking, rather than check for reward. Correspondingly, inhibition of cue-evoked NAc dopamine increased instrumental reward-seeking and decreased reward-checking behavior. Thus, transient, cue-evoked NAc core dopamine release supports reward prediction to shape reward-pursuit strategy. SIGNIFICANCE STATEMENTCues that signal reward availability can cause us to pursue reward. To ensure this is adaptive, we use the predictions these cues enable to help us decide how to pursue reward. When reward prediction is low, well seek out new reward opportunities. When it is high, well exploit the expected reward by checking for it in its usual location. Here we discovered that transient, cue-evoked nucleus accumbens dopamine fluctuations support reward predictions to shape how reward is pursued. The data show that dopamine can actually constrain reward seeking and promoting reward checking when reward is predicted strongly and imminently. These results provide new information on how dopamine shapes behavior in the moment and help understand the link between motivational and dopamine disruptions in psychiatric conditions such as addictions and depression.

neuroscience↗

bioRxiv2022

Long-term effects of THC exposure on reward learning and motivated behavior in adolescent and adult male rats

RationaleThe endocannabinoid system makes critical contributions to reward processing, motivation, and behavioral control. Repeated exposure to THC or other cannabinoid drugs can cause persistent adaptions in the endocannabinoid system and associated neural circuitry. It remains unclear how such treatments affect the way rewards are processed and pursued. Objective and methodsWe examined if repeated THC exposure (5 mg/kg/day for 14 days) during adolescence or adulthood led to long-term changes in rats capacity to flexibly encode and use action-outcome associations for goal-directed decision making. Effects on hedonic feeding and progressive ratio responding were also assessed. ResultsTHC exposure had no effect on rats ability to flexibly select actions following reward devaluation. However, instrumental contingency degradation learning, which involves avoiding an action that is unnecessary for reward delivery, was augmented in rats with a history of adult but not adolescent THC exposure. THC-exposed rats also displayed more vigorous instrumental behavior in this study, suggesting a motivational enhancement. A separate experiment found that while THC exposure had no effect on hedonic feeding behavior, it increased rats willingness to work for food on a progressive ratio schedule, an effect that was more pronounced when THC was administered to adults. Adolescent and adult THC exposure had opposing effects on the CB1-receptor dependence of progressive ratio performance, decreasing and increasing sensitivity to rimonabant-induced behavioral suppression, respectively. ConclusionsOur findings reveal that exposure to a translationally relevant THC exposure regimen induces long-lasting, age-dependent alterations in cognitive and motivational processes that regulate the pursuit of rewards.

neuroscience↗

bioRxiv2021

Cue-motivated reward seeking is negatively regulated by expected reward magnitude in Pavlovian-instrumental transfer

The Pavlovian-instrumental transfer (PIT) paradigm is widely used to assay the motivational influence of reward-predictive cues, reflected by their ability to invigorate instrumental behavior. Leading theories assume that a cues motivational properties are tied to predicted reward value. We outline an alternative view which recognizes that reward-predictive cues may suppress rather than motivate instrumental behavior under certain conditions, an effect termed positive conditioned suppression. We posit that cues signaling imminent reward delivery tend to inhibit instrumental behavior, which is exploratory by nature, in order to facilitate efficient retrieval of the expected reward. According to this view, the motivation to engage in instrumental behavior during a cue should be inversely related to the value of the predicted reward, since there is more to lose by failing to secure a high-value reward than a low-value reward. We tested this hypothesis in rats using a PIT protocol known to induce positive conditioned suppression. In Experiment 1, cues signaling different reward magnitudes elicited distinct response patterns. Whereas the 1-pellet cue increased instrumental behavior, cues signaling 3 or 9 pellets suppressed instrumental behavior and elicited high levels of food-port activity. Experiment 2 found that reward-predictive cues suppressed instrumental behavior and increased food-port activity in a flexible manner that was disrupted by post-training reward devaluation. Further analyses suggest that these findings were not driven by overt competition between the instrumental and food-port responses. We discuss how the PIT task may provide a useful tool for studying cognitive control over cue-motivated behavior in rodents.

animal behavior and cognition↗

bioRxiv2020

Reward-predictive cues elicit maladaptive reward seeking in adolescent rats

Impulsive behavior during adolescence may stem from a developmental imbalance between motivational and impulse control systems, producing greater urges to pursue reward and weakened capacities to inhibit such actions. Here, we developed a Pavlovian-instrumental transfer (PIT) protocol to assay rats’ ability to suppress cue-motivated reward seeking based on changes in reward expectancy. Traditionally, PIT studies focus on how reward-predictive cues motivate instrumental reward-seeking behavior (lever pressing). However, cues signaling imminent reward delivery also elicit countervailing focal-search responses (food-cup approach). We first examined how reward expectancy (cue-reward probability) influences expression of these competing behaviors. Adult male rats increased rates of lever pressing when presented with cues signaling lower probabilities of reward but focused their activity at the food cup on trials with cues that signaled higher probabilities of reward. We then compared adolescent and adult male rats in their responsivity to cues signaling different reward probabilities. In contrast to adults, adolescent rats did not flexibly adjust their pattern of responding based on the expected likelihood of reward delivery but increased their rate of lever pressing for both weak and strong cues. These findings indicate that impulse control over cue-motivated behavior is fundamentally dysregulated during adolescence, providing a model for studying neurobiological mechanisms of adolescent impulsivity.Competing Interest StatementThe authors have declared no competing interest.View Full Text

animal behavior and cognition↗

bioRxiv2019

Nucleus accumbens cholinergic interneurons oppose cue-motivated behavior

BackgroundEnvironmental reward-predictive stimuli provide a major source of motivation for adaptive reward pursuit behavior. This cue-motivated behavior is known to be mediated by the nucleus accumbens core (NAc). The cholinergic interneurons in the NAc are tonically active and densely arborized and, thus, well-suited to modulate NAc function. But their causal contribution to adaptive behavior remains unknown. Here we investigated the function of NAc cholinergic interneurons in cue-motivated behavior.\n\nMethodsTo do this, we used chemogenetics, optogenetics, pharmacology, and a translationally analogous Pavlovian-to-instrumental transfer behavioral task designed to assess the motivating influence of a reward-predictive cue over reward-seeking actions in male and female rats.\n\nResultsThe data show that NAc cholinergic interneuron activity is necessary and sufficient to oppose the motivating influence of appetitive cues. Chemogenetic inhibition of NAc cholinergic interneurons augmented cue-motivated behavior. Optical stimulation of acetylcholine release from NAc cholinergic interneurons prevented cues from invigorating reward-seeking behavior, an effect that was mediated by activation of {beta}2-containing nicotinic acetylcholine receptors.\n\nConclusionsThus, NAc cholinergic interneurons provide a critical regulatory influence over adaptive cue-motivated behavior and, therefore, are a potential therapeutic target for the maladaptive cue-motivated behavior that marks many psychiatric conditions, including addiction and depression.

neuroscience↗

bioRxiv2018

Chemogenetic inhibition of ventral tegmental area dopamine neurons or their inputs to the nucleus accumbens disrupts cue-triggered reward seeking but not reward taking

Reward-paired cues stimulate reward-seeking behavior through a combination of motivational and cognitive processes. We used pathway-specific chemogenetic inhibition of dopamine neurons to determine their role in the cue-elicited reward seeking, and applied a novel analytic approach to assay cue-induced changes in reward expectancy. Inhibiting ventral tegmental area dopamine neurons abolished cue-induced reward seeking but not reward retrieval, indicating that this pathway modulates response vigor but not reward expectancy. Locally inhibiting dopamine inputs to nucleus accumbens also disrupted cue-elicited reward seeking but not retrieval. Interestingly, the suppression produced by this treatment was greater in rats that responded to cues with exploratory reward seeking, without attempting to retrieve reward, than in rats exhibiting complete bouts of seeking with retrieval, indicating that individuals differ in their reliance on a dopamine-mediated motivational process. These findings shed new light on the behavioral and neural mechanisms of adaptive and compulsive forms of cue-motivated behavior.

neuroscience↗