Publications

Inhibition of dopamine neurons prevents incentive value encoding of a reward cue: With revelations from deep phenotyping

Iglesias AG, Chiu AS, Wong J, Campus P, Li F, Liu ZN, Patel SA, Deisseroth K, Akil H, Burgess CR, & Flagel SB. (2023). Inhibition of dopamine neurons prevents incentive value encoding of a reward cue: With revelations from deep phenotyping. Journal of Neuroscience, 43(44), 7376-7392. https://doi.org/10.1101/2023.05.03.539324

Abstract

The survival of an organism is dependent on their ability to respond to cues in the environment. Such cues can attain control over behavior as a function of the value ascribed to them. Some individuals have an inherent tendency to attribute reward-paired cues with incentive motivational value, or incentive salience. For these individuals, termed sign-trackers, a discrete cue that precedes reward delivery becomes attractive and desirable in its own right. Prior work suggests that the behavior of sign-trackers is dopamine-dependent, and cue-elicited dopamine in the nucleus accumbens is believed to encode the incentive value of reward cues. Here we exploited the temporal resolution of optogenetics to determine whether selective inhibition of ventral tegmental area (VTA) dopamine neurons during cue presentation attenuates the propensity to sign-track. Using male tyrosine hydroxylase (TH)-Cre Long Evans rats it was found that, under baseline conditions, ∼84% of TH-Cre rats tend to sign-track. Laser-induced inhibition of VTA dopamine neurons during cue presentation prevented the development of sign-tracking behavior, without affecting goal-tracking behavior. When laser inhibition was terminated, these same rats developed a sign-tracking response. Video analysis using DeepLabCut revealed that, relative to rats that received laser inhibition, rats in the control group spent more time near the location of the reward cue even when it was not present and were more likely to orient towards and approach the cue during its presentation. These findings demonstrate that cue-elicited dopamine release is critical for the attribution of incentive salience to reward cues.

The propensity to sign-track is associated with externalizing behavior and distinct patterns of reward-related brain activation in youth

Colaizzi JM, Flagel SB, Gearhardt AN, Borowitz MA, Kuplicki R, Zotev V, Clark G, Coronado J, Abbott T, & Paulus MP. (2023). The propensity to sign-track is associated with externalizing behavior and distinct patterns of reward-related brain activation in youth. Scientific Reports, 13(1), 4402. https://doi.org/10.1038/s41598-023-30906-3

Abstract

Externalizing behaviors in childhood often predict impulse control disorders in adulthood; however, the underlying bio-behavioral risk factors are incompletely understood. In animals, the propensity to sign-track, or the degree to which incentive motivational value is attributed to reward cues, is associated with externalizing-type behaviors and deficits in executive control. Using a Pavlovian conditioned approach paradigm, we quantified sign-tracking in 40 healthy 9–12-year-olds. We also measured parent-reported externalizing behaviors and anticipatory neural activations to outcome-predicting cues using the monetary incentive delay fMRI task. Sign-tracking was associated with attentional and inhibitory control deficits and the degree of amygdala, but not cortical, activation during reward anticipation. These findings support the hypothesis that youth with a propensity to sign-track are prone to externalizing tendencies, with an over-reliance on subcortical cue-reactive brain systems. This research highlights sign-tracking as a promising experimental approach delineating the behavioral and neural circuitry of individuals at risk for externalizing disorders.

Behavior matters for neuroscience and neuroscience matters for behavior

Vanderschuren LJMJ, Shaham Y, & Flagel SB. (2023). Behavior matters for neuroscience and neuroscience matters for behavior. Neuroscience & Biobehavioral Reviews, 144, 104963. https://doi.org/10.1016/j.neubiorev.2022.104963

Abstract

The study of behavior matters for neuroscience. The main function of the central nervous system is to integrate information from the internal and external environment, and to generate responses that facilitate survival. These adaptive responses are, by definition, both physiological and behavioral. However, maladaptive behavior can also occur, and in humans, such behavior is characteristic of psychiatric illness. Our goal, as behavioral neuroscientists, is to better understand the brain mechanisms underlying adaptive and maladaptive behaviors, and to contribute to the development of novel treatments for brain disorders. To do so effectively, we argue that behavior is critical to understanding brain function and vice versa.