Biology subjects

Paredes, N.

Publications and source records attributed to Paredes, N..

3 recordsLinked to original sources

bioRxiv2026

Dopamine projections to the basolateral amygdala enable reward prediction

Reward predictions are critical to both adaptive learning and decision making. Such predictions are supported by environmental cues that signal the availability and identity of rewarding events. Here we used fiber photometry, cell-type and pathway-specific optogenetic inhibition, Pavlovian cue-reward conditioning, and decision-making tests in male and female rats to reveal that ventral tegmental area dopamine (VTADA) projections to the basolateral amygdala (BLA) support cue-reward predictions. Reward-predictive cues trigger dopamine release in the BLA that encodes the value of the predicted reward. This cue-evoked VTADA[->]BLA activity mediates the ability of cue-reward predictions to bias action selection and adapt cue-response decisions based on the current value of the predicted reward. Cue-evoked VTADA[->]BLA activity also mediates the constraining influence of cue-reward predictions on new learning. Thus, cue-evoked BLA dopamine supports the reward predictions that both enable adaptive decision making and constrain learning.

neuroscience↗

bioRxiv2025

Striatal cell-type specific stability and reorganization underlying agency and habit

Goal-directed behavior is guided by learned action-outcome associations, allowing actions to adapt when outcomes change. With repetition, behavioral control shifts toward habit, enabling more automatic action execution, but reducing flexibility to outcome changes. Here, we used longitudinal, cellular-resolution calcium imaging, chemogenetics, instrumental conditioning, and the outcome devaluation test to ask how dorsomedial striatum D1+ and D2/A2A+ neurons contribute to the formation of goal-directed behavior and habit. DMS D1+ neurons stably encode instrumental actions, carry information about behavioral engagement and organization, and develop and maintain action-reward representational similarity and conjunctive activation with learning. Correspondingly, these neurons are critical for action-outcome learning and goal-directed decision making. In contrast, one ensemble of DMS A2A+ neurons transiently encodes actions during early action-outcome learning and another slowly starts to encode actions as habits form. Similarly, DMS A2A+ neurons transiently mediate action-outcome learning and become dispensable for goal-directed decision making. Thus, action-outcome associations are learned through DMS D1+ and A2A+ neuronal activity but only DMS D1+ neurons maintain support of adaptive, goal-directed decision making. Habit formation is associated with reorganization of A2A+ neuronal encoding. These data reveal a cell-type-specific dissociation between stable v. reorganizing striatal action representations paralleled by persistent v. transient contributions to goal-directed control.

neuroscience↗

bioRxiv2023

A dual-pathway architecture enables chronic stress to promote habit formation

Chronic stress can change how we learn and, thus, how we make decisions. Here we investigated the neuronal circuit mechanisms that enable this. Using a multifaceted systems neuroscience approach in male and female mice, we reveal a dual pathway, amygdala-striatal neuronal circuit architecture by which a recent history of chronic stress disrupts the action-outcome learning underlying adaptive agency and promotes the formation of inflexible habits. We found that the basolateral amygdala projection to the dorsomedial striatum is activated by rewarding events to support the action-outcome learning needed for flexible, goal-directed decision making. Chronic stress attenuates this to disrupt action-outcome learning and, therefore, agency. Conversely, the central amygdala projection to the dorsomedial striatum mediates habit formation. Following stress this pathway is progressively recruited to learning to promote the premature formation of inflexible habits. Thus, stress exerts opposing effects on two amygdala-striatal pathways to disrupt agency and promote habit. These data provide neuronal circuit insights into how chronic stress shapes learning and decision making, and help understand how stress can lead to the disrupted decision making and pathological habits that characterize substance use disorders and mental health conditions.

neuroscience↗