Biology subjects

Malvaez, M.

Publications and source records attributed to Malvaez, M..

6 recordsLinked to original sources

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↗

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↗

bioRxiv2024

A common stay-on-goal mechanism in anterior cingulate cortex for information and effort choices

Humans and non-humans alike often make choices to gain information, even when the information cannot be used to change the outcome. Prior research has shown the anterior cingulate cortex (ACC) is important for evaluating options involving reward-predictive information. Here we studied the role of ACC in information choices using optical inhibition to evaluate the contribution of this region during specific epochs of decision making. Rats could choose between an uninformative option followed by a cue that predicted reward 50% of the time vs. a fully informative option that signaled outcomes with certainty, but was rewarded only 20% of the time. Reward seeking during the informative S+ cue decreased following ACC inhibition, indicating a causal contribution of this region in supporting reward expectation to a cue signaling reward with certainty. Separately in a positive control experiment and in support of a known role for this region in sustaining high-effort behavior for preferred rewards, we observed reduced lever presses and lower breakpoints in effort choices following ACC inhibition. The lack of changes in reward latencies in both types of decisions indicate the motivational value of rewards remained intact, revealing instead a common role for ACC in maintaining persistence toward certain and valuable rewards. Graphical Summary O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=59 SRC="FIGDIR/small/619920v2_ufig1.gif" ALT="Figure 1"> View larger version (11K): org.highwire.dtl.DTLVardef@6fa3b2org.highwire.dtl.DTLVardef@1642fa8org.highwire.dtl.DTLVardef@74d4d9org.highwire.dtl.DTLVardef@421297_HPS_FORMAT_FIGEXP M_FIG C_FIG Significance StatementWe often make choices to gain information, even when the information cannot be used to change the outcome. Here we investigated the precise timing of the role of the anterior cingulate cortex (ACC) in decisions that involve seeking certain versus uncertain rewards. By optically inhibiting ACC neurons, we demonstrate that this region is crucial for maintaining persistence toward rewards signaled with certainty, without altering the motivational value of the reward itself. In a positive control experiment, we also confirm that ACC is important in effort-based choice. The findings reveal a common role for ACC in maintaining persistence toward certain and valuable rewards, necessary for making optimal decisions. These results have implications for understanding psychiatric disorders involving maladaptive reward-seeking behavior.

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↗

bioRxiv2018

Distinct cortical-amygdala projections drive reward value encoding and retrieval

The value of an anticipated rewarding event is crucial information in the decision to engage in its pursuit. The networks responsible for encoding and retrieving this value are largely unknown. Using glutamate biosensors and pharmacological manipulations, we found that basolateral amygdala (BLA) glutamatergic activity tracks and mediates both the encoding and retrieval of the state-dependent incentive value of a palatable food. Projection-specific and bidirectional chemogenetic and optogenetic manipulations revealed the orbitofrontal cortex (OFC) supports the BLA in these processes. Critically, the function of ventrolateral (lOFC) and medial (mOFC) OFC[->]BLA projections was found to be doubly dissociable. Whereas activity in lOFC[->]BLA projections is necessary for and sufficient to drive encoding of a positive change in the value of a reward, mOFC[->]BLA projections are necessary and sufficient for retrieving this value from memory to guide its pursuit. These data reveal a new circuit for adaptive reward valuation and pursuit, indicate dissociability in the encoding and retrieval of reward memories, and provide insight into the dysfunction in these processes that characterizes myriad psychiatric diseases.

neuroscience↗

bioRxiv2017

Habits are negatively regulated by HDAC3 in the dorsal striatum

Optimal behavior results from a balance of control between two strategies, one cognitive/goal-directed and one habitual, which rely on the anatomically distinct dorsomedial (DMS) and dorsolateral (DLS) striatum, respectively. The transcriptional regulatory mechanisms required to learn and transition between these strategies are unknown. Here we identified a critical negative regulator of habit learning. Histone deacetylase (HDAC) inhibition following instrumental conditioning accelerated habitual control of behavior. HDAC3, a transcriptional repressor, was removed from the promoters of learning-related genes in the dorsal striatum as habits formed with overtraining and with post-training HDAC inhibition. Decreasing HDAC3 function in the DLS accelerated habit formation, while DLS HDAC3 overexpression prevented habit. HDAC3 activity in the DMS was also found to constrain habit formation. These results challenge the strict dissociation between DMS and DLS function in goal-directed v. habitual behavioral control and identify dorsal striatal HDAC3 as a critical molecular substrate of the transition to habit.

neuroscience↗