Biology subjects

Wanat, M.

Publications and source records attributed to Wanat, M..

4 recordsLinked to original sources

bioRxiv2025

Nucleus accumbens dopamine encodes the trace period during appetitive Pavlovian conditioning

Pavlovian conditioning tasks have been used to identify the neural systems involved with learning cue-outcome relationships. In delay conditioning, the conditioned stimulus (CS) overlaps or co-terminates with the delivery of the unconditioned stimulus (US). Prior studies demonstrate that dopamine in the nucleus accumbens (NAc) regulates behavioral responding during delay conditioning. Furthermore, the dopamine response to the CS reflects the relative value of the upcoming reward in these tasks. In contrast to delay conditioning, trace conditioning involves a trace period separating the end of the CS and the US delivery. While dopamine has been implicated in trace conditioning, no studies have examined how NAc dopamine responds to reward-related stimuli in these tasks. Here, we developed a within-subject trace conditioning task where distinct CSs signaled either a short trace period (5s) or a long trace period (55s) prior to food reward delivery. Male rats exhibited greater conditioned responding and a faster response latency to the Short Trace CS relative to the Long Trace CS. Voltammetry recordings in the NAc found that the CS-evoked dopamine response increased on Short Trace trials but decreased on Long Trace trials. Conversely, US-evoked dopamine responses were greater on Long Trace trials relative to Short Trace trials. The CS dopamine response correlated with the response latency and not with conditioned responding. Furthermore, the relationship between CS dopamine and latency was best explained by an exponential function. Our results collectively illustrate that the trace period is encoded by the bidirectional NAc dopamine response to the CS during Pavlovian conditioning. Significance statementLearning to associate a cue with given outcome is a fundamental process underlying reward seeking behavior. Striatal dopamine is important for associating cues with rewards during Pavlovian conditioning. However, it is unclear how the dopamine system responds to cues during trace conditioning when there is temporal gap between the cue and reward. Here, we performed voltammetry recordings of striatal dopamine levels in male rats during trace conditioning. We find that cue-evoked dopamine signals encode the trace period and is related to the response latency. While prior reports find dopamine neurons signal the relative reward value by increases in dopamine levels, we demonstrate that the dopamine response to reward-predictive cues can signal the reward value through bidirectional changes in dopamine transmission.

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bioRxiv2022

Critical periods in which dopamine exerts control over behavioral responding during Pavlovian learning

RationaleLearning the association between rewards and predictive cues is critical for appetitive behavioral responding. The mesolimbic dopamine system is thought to play an integral role in establishing these cue-reward associations. The dopamine response to cues can signal differences in reward value, though this emerges only after significant training. This suggests that the dopamine system may differentially regulate behavioral responding depending on the phase of training. ObjectivesThe purpose of this study was to determine whether antagonizing dopamine receptors elicited different effects on behavior depending on the phase of training or the type of Pavlovian task. MethodsSeparate groups of male rats were trained on Pavlovian tasks in which distinct audio cues signaled either differences in reward size or differences in reward rate. The dopamine receptor antagonist flupenthixol was systemically administered prior to either the first ten sessions of training (acquisition phase) or the second ten sessions of training (expression phase) and we monitored the effect of these manipulations for an additional ten training sessions. ResultsWe identified acute effects of dopamine receptor antagonism on conditioned responding, the latency to respond, and post-reward head entries in both Pavlovian tasks. Interestingly, dopamine receptor antagonism during the expression phase produced persistent deficits in behavioral responding only in rats trained on the reward size Pavlovian task. ConclusionsTogether, our results illustrate that dopamines control over behavior in Pavlovian tasks depends upon ones prior training experience and the information signaled by the cues.

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bioRxiv2021

Enhanced preference for delayed rewards requires the basolateral amygdala and retrosplenial cortex

Sunk or irrecoverable costs imposed on a subject can impact reward-based decisions. However, it is not known if these incurred costs elicit a sustained change in reward value. To address this, we examined if sunk temporal costs subsequently alter reward consumption and reward preference in rats. We first identified the relative preference between different flavored food pellets during a free-feeding consumption test. Animals were then trained to experience the initial less preferred reward after long delays and the initial preferred reward after short delays. This training regimen enhanced the consumption and preference for the initial less desirable food reward. We probed whether this change in reward preference involved neural systems that contribute to reward valuation. Pharmacological manipulations and site-specific lesions were performed to examine the potential involvement of the dopamine system, the orbitofrontal cortex (OFC), the basolateral amygdala (BLA), and the retrosplenial cortex (RSC). The change in reward preference was unaffected by systemic dopamine receptor antagonism or OFC lesions. In contrast, lesions of the BLA or the RSC prevented the enhanced consumption and preference for the initial less desirable reward. These findings demonstrate that both the BLA and RSC participate in how sunk temporal costs alter reward value and reward preference. Significance StatementFrom an economic standpoint, only future costs should factor into ones decisions. However, behavioral evidence across species illustrates that past costs can alter decisions. The goal of this study was to identify the neural systems responsible for past costs influencing subsequent actions. We demonstrate that delivering an initially less desirable reward after long delays (high temporal costs) subsequently increases the consumption and preference for that reward. Furthermore, we identified the basolateral amygdala and the retrosplenial cortex as essential nuclei for mediating change in reward preference elicited by past temporal costs.

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bioRxiv2019

Cocaine experience abolishes the motivation suppressing effect of CRF in the ventral midbrain

Stress affects dopamine-dependent behaviors in part through the actions of corticotropin releasing factor (CRF) in the ventral tegmental area (VTA). For example, acute stress engages CRF signaling in the VTA to suppress the motivation to work for food rewards and promote drug seeking behavior. These diverging behavioral effects in food- and drug-based tasks could indicate that CRF modulates goal-directed actions in a reinforcer-specific manner. Alternatively, prior drug experience could functionally alter how CRF in the VTA regulates dopamine-dependent behavior. To address these possibilities, we examined how intra-VTA injections of CRF influenced cocaine intake and whether prior drug experience alters how CRF modulates the motivation for food rewards. Our results demonstrate that intra-VTA injections of CRF had no effect on drug intake when self-administering cocaine under a progressive ratio reinforcement schedule. We also found that a prior history of either contingent or non-contingent cocaine infusions abolished the capacity for CRF to reduce the motivation for food rewards. Furthermore, voltammetry recordings in the nucleus accumbens illustrate that CRF in the VTA had no effect on cocaine-evoked dopamine release. These results collectively illustrate that exposure to abused substances functionally alters how neuropeptides act within the VTA to influence motivated behavior.

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