Biology subjects

Faraji, M.

Publications and source records attributed to Faraji, M..

6 recordsLinked to original sources

bioRxiv2026

Ventral tegmental area dopamine neuron activity mediates multi-valent outcomes during decision making under risk of punishment

Dopamine contributes to reward-related decision making, but its contributions to decision contexts that include explicit punishment are less well understood. To elucidate the role of ventral tegmental area (VTA) dopamine neurons in decision making under risk of punishment, we used fiber photometry to record activity in these neurons during a decision-making task in which rats choose between a small, "safe" reward and a large reward associated with varying probabilities of explicit punishment. Dopamine neuron activity exhibited phasic increases during risky "Wins" (reward without punishment) and phasic decreases during risky "Losses" (reward plus punishment), each of which scaled with punishment probability and intensity. Further analyses revealed that this outcome-evoked activity predicted choices on subsequent trials. To determine whether VTA dopamine neuron activity plays a causal role in these risk-based decisions, we used optogenetics to selectively inhibit these neurons during risky Wins and Losses. Inhibition of VTA dopamine neurons during Wins selectively reduced the frequency of risky choices after a Win, whereas inhibition during Losses selectively reduced the frequency of risky choices after a Loss. These data reveal that VTA dopamine neuron activity during outcome receipt is causally related to subsequent decision-making behavior. In addition, the fact that the effects of inhibition on choice behavior were specific to the outcome with which the inhibition was paired suggests that VTA dopamine neuron activity contributes to updating after Wins and Losses independently. Significance StatementDopamine is implicated in movement, motivation, and learning, and has been strongly linked with substance use and risk-seeking behavior. Despite these associations, it is unclear how the activity of dopamine neurons influences decision making under risk of punishment. To elucidate this, we recorded from ventral tegmental area (VTA) dopamine neurons and found that their activity at the population level integrates reward alongside the probability and intensity of punishment experienced during risky outcomes. Further, inhibition of VTA dopamine neuron activity during risky outcomes decreased risk-seeking behavior in an outcome-specific manner. Our findings align with models suggesting that VTA dopamine neurons signal prediction errors, and provide insight into the role of these neurons in adaptive decision making.

neuroscience↗

bioRxiv2025

A novel cost-benefit decision-making task involving cued punishment; effects of sex and psychostimulant administration

Chronic substance use is associated with alterations in multiple forms of cost-benefit decision making, which may prolong and exacerbate continued use. Cues that predict reward can cause substantial shifts in a variety of reward-directed behavior, including decision making. In contrast, how decision making is modulated by cues predictive of punishment is much less well understood. To begin to address these issues, male and female Long-Evans rats were tested in a novel decision-making task in which they chose between a small, "safe" reward and a large reward that was punished by a mild footshock when it was preceded by a probabilistically delivered cue prior to the choice. Rats of both sexes were sensitive to the cue, preferring the large reward in the absence of the cue but the small reward in the presence of the cue. Acute systemic amphetamine reduced choice of the large reward and diminished the efficacy of the cue in guiding choice behavior. Chronic cocaine led to divergent patterns of cue insensitivity in males and females; males increased choice of the large reward on cued trials, whereas females increased avoidance of the large reward on uncued trials. Similar to acute amphetamine, acute systemic administration of the D2/3 dopamine receptor agonist bromocriptine reduced preference for the large reward across all groups. These findings highlight the contributions of punishment cues to decision making, as well as the importance of sex as a biological variable in investigating cognitive alterations caused by chronic substance use.

neuroscience↗

bioRxiv2025

Optogenetic inhibition reveals distinct contributions of medial prefrontal cortex to intertemporal choice in young and aged rats

The ability to choose adaptively between rewards differing in magnitude and delay (intertemporal choice) is critical for numerous life outcomes. Compared to younger adults, older adults tend to exhibit greater preference for large, delayed over small, immediate rewards (i.e., less delay discounting), which could lead to missed opportunities to obtain resources necessary for quality of life. Intertemporal choice is mediated by the prefrontal cortex, but how this is impacted by advanced age is not well understood. We used optogenetic inactivation to investigate contributions of medial prefrontal cortex (mPFC) during distinct components of an intertemporal choice task in young and aged rats. mPFC inactivation during deliberation (during decisions between small, immediate vs. large, delayed rewards) increased preference for large, delayed rewards in both age groups. In contrast, inactivation during delays prior to large reward delivery increased preference for large, delayed rewards only in aged rats. Choices were unaffected by inactivation during other task phases. Results suggest that mPFC integrates information regarding anticipated outcomes into the decision process across the whole lifespan, but that only in aging is mPFC critical for consolidating information regarding reward delays into the decision structure in order to modulate choice behavior.

neuroscience↗

bioRxiv2024

Effects of systemic oxytocin receptor activation and blockade on risky decision making in female and male rats

The neuropeptide oxytocin is traditionally known for its roles in parturition, lactation, and social behavior. Other data, however, show that oxytocin can modulate behaviors outside of these contexts, including drug self-administration and some aspects of cost-benefit decision making. Here we used a pharmacological approach to investigate the contributions of oxytocin signaling to decision making under risk of explicit punishment. Female and male Long-Evans rats were trained on a risky decision-making task in which they chose between a small, "safe" food reward and a large, "risky" food reward that was accompanied by varying probabilities of mild footshock. Once stable choice behavior emerged, rats were tested in the task following acute intraperitoneal injections of oxytocin or the oxytocin receptor antagonist L-368,899. Neither drug affected task performance in males. In females, however, both oxytocin and L-368,899 caused a dose-dependent reduction in preference for large risky reward. Control experiments showed that these effects could not be accounted for by alterations in food motivation or shock sensitivity. Together, these results reveal a sex-dependent effect of oxytocin signaling on risky decision making in rats.

neuroscience↗

bioRxiv2023

Effects of Reproductive Experience on Cost-Benefit Decision Making in Females and Males

Almost all individuals undergo reproductive and/or parenting experience at some point in their lives, and pregnancy and childbirth in particular are associated with alterations in the prevalence of several psychiatric disorders. Research in rodents shows that maternal experience affects spatial learning and other aspects of hippocampal function. In contrast, there has been little work in animal models concerning how reproductive experience affects cost-benefit decision making, despite the relevance of this aspect of cognition for psychiatric disorders. To begin to address this issue, reproductively experienced (RE) and reproductively naive (RN) female and male Long-Evans rats were tested across multiple tasks that assess different forms of cost-benefit decision making. In a risky decision-making task, in which rats chose between a small, safe food reward and a large food reward accompanied by variable probabilities of punishment, RE and RN males did not differ, whereas RE females chose the large risky reward significantly more frequently than RN females (greater risk taking). In an intertemporal choice task, in which rats chose between a small, immediate food reward and a large food reward delivered after a variable delay period, RE males chose the large reward more frequently than RN males, whereas RE females chose the large reward less frequently than RN females. Together, these results show distinct effects of reproductive experience on different forms of cost-benefit decision making in rats of both sexes, and highlight reproductive status as a variable that could influence aspects of cognition relevant for psychiatric disorders.

animal behavior and cognition↗

bioRxiv2021

Adolescent dopamine neurons represent reward differently during action and state guided learning

The neuronal underpinning of learning cause-and-effect associations in the adolescent brain remains poorly understood. Two fundamental forms of associative learning are Pavlovian (classical) conditioning, where a stimulus is followed by an outcome, and operant (instrumental) conditioning, where outcome is contingent on action execution. Both forms of learning, when associated with a rewarding outcome, rely on midbrain dopamine neurons in the ventral tegmental area (VTA) and substantia nigra (SN). We find that in adolescent male rats, reward-guided associative learning is encoded differently by midbrain dopamine neurons in each conditioning paradigm. Whereas simultaneously recorded VTA and SN adult neurons have a similar phasic response to reward delivery during both forms of conditioning, adolescent neurons display a muted reward response during operant but a profoundly larger reward response during Pavlovian conditioning suggesting that adolescent neurons assign a different value to reward when it is not gated by action. The learning rate of adolescents and adults during both forms of conditioning was similar further supporting the notion that differences in reward response in each paradigm are due to differences in motivation and independent of state versus action value learning. Static characteristics of dopamine neurons such as dopamine cell number and size were similar in the VTA and SN but there were age differences in baseline firing rate, stimulated release and correlated spike activity suggesting that differences in reward responsiveness by adolescent dopamine neurons are not due to differences in intrinsic properties of these neurons but engagement of different networks.

neuroscience↗