Biology subjects

Lefner, M. J.

Publications and source records attributed to Lefner, M. J..

6 recordsLinked to original sources

bioRxiv2024

Reward and punishment contingency shifting reveals distinct roles for VTA dopamine and GABA neurons in behavioral flexibility

In dynamic environments where stimuli predicting rewarding or aversive outcomes unexpectedly change, it is critical to flexibly update behavior while preserving recollection of previous associations. Dopamine and GABA neurons in the ventral tegmental area (VTA) are implicated in reward and punishment learning, yet little is known about how each population adapts when the predicted outcome valence changes. We measured VTA dopamine and GABA population activity while male and female rats learned to associate three discrete auditory cues to three distinct outcomes: reward, punishment, or no outcome within the same session. After learning, the reward and punishment cue-outcome contingencies were reversed, and subsequently rereversed. As expected, the dopamine population rapidly adapted to learning and contingency reversals by increasing the response to appetitive stimuli and decreasing the response to aversive stimuli. In contrast, the GABA population increased activity to all sensory events regardless of valence, including the neutral cue. Reversing learned contingencies selectively influenced GABA responses to the reward-predictive cue, prolonging increased activity within and across sessions. The observed valence-specific dissociations in the directionality and temporal progression of VTA dopamine and GABA calcium activity indicates that these populations are independently recruited and serve distinct roles during appetitive and aversive associative learning and contingency reversal.

neuroscience↗

bioRxiv2021

Sex differences in behavioral responding and dopamine release during early Pavlovian learning

Learning associations between cues and rewards requires the mesolimbic dopamine system. The dopamine response to cues signals differences in reward value in well-trained animals. However, these value-related dopamine responses are absent during early training sessions when cues signal differences in the reward rate. These findings suggest cue-evoked dopamine release conveys differences between outcomes only after extensive training, though it is unclear if this is unique to when cues signal differences in reward rate, or if this is also evident when cues signal differences in other value-related parameters such as reward size. To address this, we utilized a Pavlovian conditioning task in which one audio cue was associated with a small reward (one pellet) and another audio cue was associated with a large reward (three pellets). We performed fast-scan cyclic voltammetry to record changes in dopamine release in the nucleus accumbens of male and female rats throughout learning. While female rats exhibited higher levels of conditioned responding, a faster latency to respond, and elevated post-reward head entries relative to male rats, there were no sex differences in the dopamine response to cues. Multiple training sessions were required before cue-evoked dopamine release signaled differences in reward size. Reward-evoked dopamine release scaled with reward size, though females displayed lower reward-evoked dopamine responses relative to males. Conditioned responding related to the decrease in the peak reward-evoked dopamine response and not to cue-evoked dopamine release. Collectively these data illustrate sex differences in behavioral responding as well as in reward-evoked dopamine release during Pavlovian learning.

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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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bioRxiv2020

Dopamine release and its control over early Pavlovian learning differs between the NAc core and medial NAc shell

Dopamine neurons respond to cues to reflect the value of associated outcomes. These cue-evoked dopamine responses can encode the relative rate of reward in rats with extensive Pavlovian training. Specifically, a cue that always follows the previous reward by a short delay (high reward rate) evokes a larger dopamine response in the nucleus accumbens (NAc) core relative to a distinct cue that always follows the prior reward by a long delay (low reward rate). However, it was unclear if these reward rate dopamine signals are evident during early Pavlovian training sessions and across NAc subregions. To address this, we performed fast-scan cyclic voltammetry recordings of dopamine levels to track the pattern of cue- and reward-evoked dopamine signals in the NAc core and medial NAc shell. We identified regional differences in the progression of cue-evoked dopamine signals across training. However, the dopamine response to cues did not reflect the reward rate in either the NAc core or the medial NAc shell during early training sessions. Pharmacological experiments found that dopamine-sensitive conditioned responding emerged in the NAc core before the medial NAc shell. Together, these findings illustrate regional differences in NAc dopamine release and its control over behavior during early Pavlovian learning.

neuroscience↗

bioRxiv2019

Changes in subjective preference do not require dopamine signaling or the orbital frontal cortex

Sunk or unrecoverable costs impact proximal reward-based decisions across species. However, it is not known if these incurred costs elicit a long-lasting change in reward value. To address this, we identified the relative preference between different flavored food pellets in rats. Animals were then trained to experience the initially preferred reward after short delays and the initially less preferred reward after long delays. This training regimen enhanced the preference for the initially less desirable food reward. We probed whether this change in subjective preference involved dopamine signaling or the orbital frontal cortex (OFC) given that these neural systems contribute to reward valuation. Systemic dopamine receptor antagonism attenuated anticipatory responding during training sessions but did not prevent the change in reward preference elicited by incurred temporal costs. OFC lesions had no effect on anticipatory responding during training or on the change in reward preference. These findings collectively illustrate that the neural systems involved with economic assessments of reward value are not contributing to changes in subjective preference.

neuroscience↗

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.

neuroscience↗