Boosting of Thalamic D2 Dopaminergic Transmission: A Potential Strategy for Drug-Seeking Attenuation

Monte, Fabricio H Do; Kirouac, Gilbert J.

doi:10.1523/eneuro.0378-17.2017

Cited by 8 publications

(7 citation statements)

References 49 publications

(86 reference statements)

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“…Indeed, the posterior PVT has recently been referred to as both a potential ''stressmemory'' center of the brain (Bhatnagar and Dallman, 1998;Bhatnagar et al, 2000;Fenoglio et al, 2006;Heydendael et al, 2011) and the whole nucleus as the ''traffic light of motivated behaviors'' (McGinty and Otis, 2020). The past decade has seen multiple review articles and commentaries describing the heterogeneity of PVT anatomy, diverse neurochemistry, and functions (James and Dayas, 2013;Do-Monte and Kirouac, 2017;Millan et al, 2017;Barson et al, 2020), including a potential role in long-term fear memory (Padilla-Coreano et al, 2012;Penzo et al, 2015;Do-Monte et al, 2016), salience, conflict resolution (Choi and McNally, 2017;Choi et al, 2019), motivated memory, and associated behaviors (Kirouac, 2015;Millan et al, 2017;Zhu et al, 2018;Zhou and Zhu, 2019;Lucantonio et al, 2020). However, given its small size [e.g., ∼7 mm 3 for left paraventricular nucleus (Krauth et al, 2010;Jo et al, 2019)], there is a dearth in our understanding of PVT function in the human brain.…”

Section: Introductionmentioning

confidence: 99%

Functional Connectivity of the Human Paraventricular Thalamic Nucleus: Insights From High Field Functional MRI

Kark

Birnie

Baram

et al. 2021

Front. Integr. Neurosci.

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The paraventricular thalamic nucleus (PVT) is a small but highly connected nucleus of the dorsal midline thalamus. The PVT has garnered recent attention as a context-sensitive node within the thalamocortical arousal system that modulates state-dependent motivated behaviors. Once considered related to generalized arousal responses with non-specific impacts on behavior, accumulating evidence bolsters the contemporary view that discrete midline thalamic subnuclei belong to specialized corticolimbic and corticostriatal circuits related to attention, emotions, and cognition. However, the functional connectivity patterns of the human PVT have yet to be mapped. Here, we combined high-quality, high-resolution 7T and 3T resting state MRI data from 121 young adult participants from the Human Connectome Project (HCP) and thalamic subnuclei atlas masks to investigate resting state functional connectivity of the human PVT. The 7T results demonstrated extensive positive functional connectivity with the brainstem, midbrain, ventral and dorsal medial prefrontal cortex (mPFC), anterior and posterior cingulate, ventral striatum, hippocampus, and amygdala. These connections persist upon controlling for functional connectivity of the rest of the thalamus. Whole-brain contrasts provided further evidence that, compared to three nearby midline thalamic subnuclei, functional connectivity of the PVT is strong with the hippocampus, amygdala, ventral and dorsal mPFC, and middle temporal gyrus. These findings suggest that, even during rest, the human PVT is functionally coupled with many regions known to be structurally connected to rodent and non-human primate PVT. Further, cosine similarity analysis results suggested the PVT is integrated into the default mode network (DMN), an intrinsic connectivity network associated with episodic memory and self-referential thought. The current work provides a much-needed foundation for ongoing and future work examining the functional roles of the PVT in humans.

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Section: Introductionmentioning

confidence: 99%

Functional Connectivity of the Human Paraventricular Thalamic Nucleus: Insights From High Field Functional MRI

Kark

Birnie

Baram

et al. 2021

Front. Integr. Neurosci.

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“…For these studies, the effects of PrL-PVT manipulation were examined early in Pavlovian training, when Pavlovian cues are known to evoke a DA response in the NAc to a different degree in STs and GTs 28,56 . Although we expected to observe more robust behavioral effects during this period, we found that stimulation of the PrL-PVT pathway early in Pavlovian training did not affect the behavior of STs, nor did it significantly affect extracellular It has become increasingly apparent in recent years that the PVT and its associated circuitry play an important role in motivated behaviors, including those related to addiction and anxiety-related disorders 16,33,[57][58][59][60][61][62][63][64][65][66][67][68] . Here, we honed in on the PrL-PVT pathway and exploited an animal model of individual differences in cue-reward learning to demonstrate that this circuit acts as a top-down control mechanism to suppress the attribution of incentive value to a food-paired cue.…”

Section: Discussionmentioning

confidence: 72%

The Paraventricular Thalamus is a Critical Mediator of Top-down Control of Cue-motivated Behavior in Rats

Campus

Covelo

Kim

et al. 2019

Preprint

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Stimuli or cues in the environment can elicit complex emotional states, and thereby maladaptive behavior, as a function of their ascribed value. Here we capture individual variation in the propensity to attribute motivational value to reward-cues using the signtracker/goal-tracker animal model. Goal-trackers attribute predictive value to rewardcues, and sign-trackers attribute both predictive and incentive value. Using chemogenetics and microdialysis, we show that, in sign-trackers, stimulation of the neuronal pathway from the prelimbic cortex (PrL) to the paraventricular nucleus of the thalamus (PVT) decreases the incentive value of a reward-cue. In contrast, in goaltrackers, inhibition of the PrL-PVT pathway increases both the incentive value and dopamine levels in the nucleus accumbens shell. The PrL-PVT pathway, therefore, exerts top-down control over the dopamine-dependent process of incentive salience attribution. These results highlight PrL-PVT pathway as a potential target for treating psychopathologies associated with the attribution of excessive incentive value to reward-cues, including addiction. independent delivery of food-US, distinct conditioned responses emerge. Some rats, goal-trackers (GTs), approach the location of impending food delivery upon the lever-CS presentation, while others, sign-trackers (STs), approach and interact with the lever-CS itself. For both GTs and STs the lever-CS acquires predictive value and elicits a conditioned response, but for STs, the CS also acquires incentive value. This animal model, therefore, provides a unique platform to investigate the neurobiological determinants of individual differences in the propensity to attribute incentive salience to reward-cues.Previous studies suggest that sign-tracking behavior results from enhanced activity in subcortical brain circuits known to mediate motivated behaviors, including the striatal dopamine system, the amygdala, and the hypothalamus 22,23,28-31 . In addition, relative to GTs, STs appear to have deficits in top-down cognitive control originating in the prefrontal cortex 32 . Thus, we hypothesize that sign-tracking behavior arises from an imbalance between top-down cognitive control and bottom-up motivational processes.One brain region that is ideally situated to act as a fulcrum between cortical, limbic and homeostatic circuits is the paraventricular nucleus of the thalamus (PVT). The PVT has, in fact, come to be known as the "thalamic gateway" 33 for appetitive motivation; acting to integrate cognitive, emotional, motivational and viscerosensitive information, and, in turn, guide behavioral responses 33,34 . Consistent with this view, the PVT has been implicated in the propensity to attribute incentive motivational value to reward-cues [35][36][37] .The functional connectivity of the PVT in response to cue-induced neuronal activity differentiates STs from GTs 28,29,35 . In STs, cue-induced activity in the PVT is correlated with activity in subcortical areas, including the nucleus accumbens (NAc); whereas in GTs, cue-...

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“…It has become increasingly apparent in recent years that the PVT and its associated circuitry play an important role in motivated behaviors, including those related to addiction and anxiety-related disorders (Coffey et al, 2010; Do-Monte et al, 2015; Matzeu et al, 2015; Zhu et al, 2016; Choi and McNally, 2017; Do-Monte and Kirouac, 2017b; Do-Monte et al, 2017a; Matzeu et al, 2017; Millan et al, 2017; Otis et al, 2017; Beas et al, 2018; Giannotti et al, 2018; Zhu et al, 2018; Choi et al, 2019). Here, we honed in on the PrL-PVT pathway and exploited an animal model of individual differences in cue-reward learning to demonstrate that this circuit acts as a top-down control mechanism to suppress the attribution of incentive value to a food-paired cue.…”

Section: Discussionmentioning

confidence: 99%

The paraventricular thalamus is a critical mediator of top-down control of cue-motivated behavior in rats

Campus

Covelo

Kim

et al. 2019

eLife

View full text Add to dashboard Cite

Cues in the environment can elicit complex emotional states, and thereby maladaptive behavior, as a function of their ascribed value. Here we capture individual variation in the propensity to attribute motivational value to reward-cues using the sign-tracker/goal-tracker animal model. Goal-trackers attribute predictive value to reward-cues, and sign-trackers attribute both predictive and incentive value. Using chemogenetics and microdialysis, we show that, in sign-trackers, stimulation of the neuronal pathway from the prelimbic cortex (PrL) to the paraventricular nucleus of the thalamus (PVT) decreases the incentive value of a reward-cue. In contrast, in goal-trackers, inhibition of the PrL-PVT pathway increases both the incentive value and dopamine levels in the nucleus accumbens shell. The PrL-PVT pathway, therefore, exerts top-down control over the dopamine-dependent process of incentive salience attribution. These results highlight PrL-PVT pathway as a potential target for treating psychopathologies associated with the attribution of excessive incentive value to reward-cues, including addiction.

show abstract

Boosting of Thalamic D2 Dopaminergic Transmission: A Potential Strategy for Drug-Seeking Attenuation

Cited by 8 publications

References 49 publications

Functional Connectivity of the Human Paraventricular Thalamic Nucleus: Insights From High Field Functional MRI

Functional Connectivity of the Human Paraventricular Thalamic Nucleus: Insights From High Field Functional MRI

The Paraventricular Thalamus is a Critical Mediator of Top-down Control of Cue-motivated Behavior in Rats

The paraventricular thalamus is a critical mediator of top-down control of cue-motivated behavior in rats

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