Environmental cues associated with rewards like food can acquire motivational value themselves, resulting in the initiation of reward-seeking behaviors upon subsequent cue presentations. These goal-directed behaviors are not acquired through incremental trial-and-error learning, but arise from an interaction between current states and learned associations. A key example is salt appetite. Rats that have learned to associate a cue with an aversively concentrated salt taste will respond to the cue and seek out salt if they are sodium-depleted, even before salt has ever been experienced as positive. Little is known about how cues and goals can acquire value in such a drastic manner before a prediction error can occur (i.e., when salt is first tasted in a sodium-deprived state). The proposed research will investigate the neural circuitry of adaptive salt-seeking behavior using this striking phenomenon as a model. Previous work has shown that neurons of the ventral pallidum (VP), which is bidirectionally connected to other reward circuit regions including the nucleus accumbens (NAc) and ventral tegmental area (VTA), activate to salt-paired cues and salt itself following sodium deprivation in a similar manner to sucrose-paired cues and sucrose. Although these VP neural dynamics correlate with the behaviorally-relevant shifts in the value of cues and rewards, it is unknown whether VP dynamics are necessary for salt-seeking behavior, nor how NAc and dopamine inputs to VP regulate its activity and the valuation of cues. The proposed studies will use optogenetic tools, new viral vectors, and transgenic TH-Cre rats to investigate the effects of temporarily inhibiting VP (Aim 1), the NAc-VP pathway (Aim 2), and dopaminergic VTA inputs to NAc or VP (Aim 3) on adaptive salt-seeking behavior and salt reward following sodium deprivation. In addition, Aims 2 and 3 include simultaneous tetrode recordings of VP (Aim 2) and NAc or VP (Aim 3) to uncover how patterns of activity related to goal seeking arise. The proposed studies will provide fresh insight into the neural mechanisms of adaptive goal-seeking behaviors, and could substantially update our understanding of disorders of reward dysfunction including depression, obesity, and compulsive behaviors. These disorders are characterized by hypo- or hyper-reactivity to cues and motivational problems, and are thought to involve VTA-NAc-VP dysfunction. Moreover, such problems often arise as immediate changes in motivation due to a change in state, such as stress or drug priming, a feature not easily explained by current incremental learning and prediction-error models. By applying new techniques and behavioral paradigms to study mechanisms of how such immediate changes in goal-seeking occur in the brain, the work carries great potential for updating our understanding of how disorders of the reward system arise.
The proposed studies have the potential to provide novel insights to models of learning and decision making. Understanding how brain reward circuitry, which is homologous in rodents and humans, is involved in adaptive goal-seeking behavior will be helpful in understanding how the same neural circuitry is involved in the development of maladaptive goal-seeking behaviors that can lead to disorders of reward dysfunction including depression, obesity, and addiction. The use of new technologies to understand brain function, and a paradigm related to human cue-reactivity, will make the results translatable to psychiatric conditions, potentially aiding novel clinical interventions.
| Chang, Stephen E; Todd, Travis P; Smith, Kyle S (2018) Paradoxical accentuation of motivation following accumbens-pallidum disconnection. Neurobiol Learn Mem 149:39-45 |
| Chang, Stephen E; Smith, Kyle S (2018) Context-driven Salt Seeking Test (Rats). Bio Protoc 8: |
| Chang, Stephen E; Smedley, Elizabeth B; Stansfield, Katherine J et al. (2017) Optogenetic Inhibition of Ventral Pallidum Neurons Impairs Context-Driven Salt Seeking. J Neurosci 37:5670-5680 |
| Chang, Stephen E; Smith, Kyle S (2016) An omission procedure reorganizes the microstructure of sign-tracking while preserving incentive salience. Learn Mem 23:151-5 |
| Chang, Stephen E; Todd, Travis P; Bucci, David J et al. (2015) Chemogenetic manipulation of ventral pallidal neurons impairs acquisition of sign-tracking in rats. Eur J Neurosci 42:3105-16 |
