Lesions of the paraventricular nucleus of the thalamus differentially affect sign- and goal-tracking conditioned responses

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Abstract

<p class="first" id="P1">Recently evidence has emerged suggesting a role for the paraventricular nucleus of the thalamus (PVT) in the processing of reward-associated cues. However, the specific role of the PVT in these processes has yet to be elucidated. Here we use an animal model that captures individual variation in response to discrete reward-associated cues to further assess the role of the PVT in stimulus-reward learning. When rats are exposed to a Pavlovian conditioning paradigm, wherein a discrete cue predicts food reward, two distinct conditioned responses emerge. Some rats, termed sign-trackers, approach and manipulate the cue; whereas others, termed goal-trackers, approach the location of reward delivery upon cue presentation. For both sign- and goal-trackers the cue is a predictor; but only for sign-trackers is it also an incentive stimulus. We investigated the role of the PVT in the acquisition and expression of these conditioned responses using an excitotoxic lesion. Results indicate that PVT lesions prior to acquisition amplify the differences between phenotypes—increasing sign-tracking and attenuating goal-tracking behavior. Lesions of the PVT after rats had acquired their respective conditioned responses also attenuated the expression of the goal-tracking response, and increased the sign-tracking response, but did so selectively in goal-trackers. These results suggest that the PVT acts to suppress the attribution of incentive salience to reward cues, as disruption of the functional activity within this structure enhances the tendency to sign-track. </p>

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A selective role for dopamine in reward learning

Shelly Flagel, Jeremy Clark, Terry E Robinson … (2010)

Individuals make choices and prioritize goals using complex processes that assign value to rewards and associated stimuli. During Pavlovian learning, previously neutral stimuli that predict rewards can acquire motivational properties, whereby they themselves become attractive and desirable incentive stimuli. But individuals differ in whether a cue acts solely as a predictor that evokes a conditional response, or also serves as an incentive stimulus, and this determines the degree to which a cue might bias choice or even promote maladaptive behavior. Here we use rats that differ in the incentive motivational properties they attribute to food cues to probe the role of the neurotransmitter dopamine in stimulus-reward learning. We show that intact dopamine transmission is not required for all forms of learning in which reward cues become effective predictors. Rather, dopamine acts selectively in a form of reward learning in which “incentive salience” is assigned to reward cues. In individuals with a propensity for this form of learning, reward cues come to powerfully motivate and control behavior. This work provides insight into the neurobiology of a form of reward learning that confers increased susceptibility to disorders of impulse control.

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Prefrontal-striatal pathway underlies cognitive regulation of craving.

Hedy Kober, Peter Mende-Siedlecki, Ethan F Kross … (2010)

The ability to control craving for substances that offer immediate rewards but whose long-term consumption may pose serious risks lies at the root of substance use disorders and is critical for mental and physical health. Despite its importance, the neural systems supporting this ability remain unclear. Here, we investigated this issue using functional imaging to examine neural activity in cigarette smokers, the most prevalent substance-dependent population in the United States, as they used cognitive strategies to regulate craving for cigarettes and food. We found that the cognitive down-regulation of craving was associated with (i) activity in regions previously associated with regulating emotion in particular and cognitive control in general, including dorsomedial, dorsolateral, and ventrolateral prefrontal cortices, and (ii) decreased activity in regions previously associated with craving, including the ventral striatum, subgenual cingulate, amygdala, and ventral tegmental area. Decreases in craving correlated with decreases in ventral striatum activity and increases in dorsolateral prefrontal cortex activity, with ventral striatal activity fully mediating the relationship between lateral prefrontal cortex and reported craving. These results provide insight into the mechanisms that enable cognitive strategies to effectively regulate craving, suggesting that it involves neural dynamics parallel to those involved in regulating other emotions. In so doing, this study provides a methodological tool and conceptual foundation for studying this ability across substance using populations and developing more effective treatments for substance use disorders.