Unresponsive Choline Transporter as a Trait Neuromarker and a Causal Mediator of Bottom-Up Attentional Biases

Cherian, Ajeesh Koshy; Kucinski, Aaron; Pitchers, Kyle K.; Yegla, Brittney; Parikh, Vinay; Kim, Youngsoo; Valuskova, Paulina; Gurnani, Sarika; Lindsley, Craig W.; Blakely, Randy D.; Sarter, Martin

doi:10.1523/jneurosci.3499-16.2017

Cited by 37 publications

(74 citation statements)

References 69 publications

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“…In these rats, inhibition of the PrL-PVT pathway is without effect because the relative predominance of bottom-up processes remains intact. In contrast, in GTs, top-down processes appear to dominate over subcortical processes 29,32,52 . As a result, GTs are more goal-driven and more inclined to attribute predictive, but not incentive, value to reward-cues.…”

Section: Discussionmentioning

confidence: 91%

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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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Section: Discussionmentioning

confidence: 91%

“…During all PavCA training sessions rats were tethered to a swivel arm to habituate them to the microdialysis procedures. In this experiment, rats were phenotyped as STs or GTs following 3 initial PavCA sessions 52 , and subsequently received CNO or VEH 25 minutes prior to the remaining PavCA training sessions (sessions 4-6). Fig.…”

Section: Experiments 2 Methodsmentioning

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

Preprint

Self Cite

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“…Stimulation was expected to increase CHT density in the plasma membrane-enriched LP1 fraction, reflecting mobilization from intracellular domains to synaptosomal plasma membrane. However, this was only the case for GTs, but not for STs (Koshy Cherian et al, 2017). …”

Section: Unresponsive Chts In Stsmentioning

confidence: 89%

“…As already noted, basal levels of cortical ACh release do not differ between the phenotypes. Potassium-stimulation-induced ACh levels in GTs reached 201.81 ± 27.28% over baseline compared with 109.07 ± 20.83% in STs (Koshy Cherian et al, 2017). In contrast to ACh, GABA, glutamate, serotonin, dopamine, and norepinephrine levels were not differently stimulated in STs and GTs.…”

Section: Attention-associated Levels Of Cholinergic Neuromodulation Imentioning

confidence: 89%

“…In contrast, GTs also learn about the cue, as indicated by orienting responses, but their cue-driven behavior is goal-directed, toward the location of impending pellet delivery. Poor attentional control and a propensity for attribution of incentive salience are hypothesized to be overlapping and complementary expressions of the cognitive-motivational styles that are indexed by “sign-tracking” (Koshy Cherian et al, 2017). In STs, orienting and approaching a CS initially may primarily be a result of the attentional bias but, over time, the power of the cue to control behavior and to serve as a conditioned reinforcer likely involves the attribution of incentive salience, rendering the CS attractive and magnetic.…”

Section: Cht Inhibition Causes Sign-trackingmentioning

confidence: 99%

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The neuroscience of cognitive-motivational styles: Sign- and goal-trackers as animal models.

Sarter

Phillips

2018

Behavioral Neuroscience

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Cognitive-motivational styles describe predominant patterns of processing or biases that broadly influence human cognition and performance. Here we focus on the impact of cognitive-motivational styles on the response to cues predicting the availability of food or addictive drugs. An individual may preferably conduct an analysis of the motivational significance of reward cues, with the result that such cues per se are perceived as rewarding and worth approaching and working for. Alternatively, a propensity for a “cold” analysis of the behavioral utility of a reward cue may yield search behavior for food or drugs but not involve cue approach. Animal models for studying the neuronal mechanisms mediating such styles have originated from research concerning behavioral indices that predict differential vulnerability to addiction-like behaviors. Rats classified as sign- or goal-trackers (STs, GTs) were found to have opposed attentional biases (bottom-up or cue-driven attention vs. top-down or goal-driven attentional control) that are mediated primarily via relatively unresponsive versus elevated levels of cholinergic neuromodulation in the cortex. The capacity for cholinergic neuromodulation in STs is limited by a neuronal choline transporter (CHT) that fails to support increases in cholinergic activity. Moreover, in contrast to STs, the frontal dopamine system in GTs does not respond to the presence of drug cues and, thus, biases against cue-oriented behavior. The opponent cognitive-motivational styles that are indexed by sign- and goal-tracking bestow different cognitive–behavioral vulnerabilities that may contribute to the manifestation of a wide range of neuropsychiatric disorders.

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Comment on Pohorala et al.: Sign-tracking as a predictor of addiction vulnerability

2021

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Unresponsive Choline Transporter as a Trait Neuromarker and a Causal Mediator of Bottom-Up Attentional Biases

Cited by 37 publications

References 69 publications

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

The neuroscience of cognitive-motivational styles: Sign- and goal-trackers as animal models.

Comment on Pohorala et al.: Sign-tracking as a predictor of addiction vulnerability

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