Connections of the XXXX Orbitofrontal Cortex and Regulation of Goal-Directed Action Selection by @entity9140 .

@entity9140 @entity550 @entity22636 @entity19 @entity21537 @entity4149
BACKGROUND: Distinguishing between actions that are more likely or less likely to be rewarded is a critical aspect of goal-directed decision making. However, neuroanatomic and molecular mechanisms are not fully understood. METHODS: We used anterograde tracing, viral-mediated gene silencing, functional disconnection strategies, pharmacologic rescue, and designer receptors exclusively activated by designer drugs (DREADDs) to determine the anatomic and functional connectivity between the @entity550 ( @entity550 ) and the amygdala in @entity19 . In particular, we knocked down @entity9140 ( @entity9140 ) bilaterally in the @entity550 or generated an @entity550 "disconnection" by pairing unilateral @entity550 @entity9140 knockdown with lesions of the contralateral amygdala. We characterized decision-making strategies using a task in which @entity19 selected actions based on the likelihood that they would be reinforced. Additionally, we assessed the effects of DREADD-mediated @entity550 inhibition on the consolidation of action-outcome conditioning. RESULTS: As in other species, the @entity550 projects to the basolateral amygdala and dorsal striatum in @entity19 . Bilateral @entity9140 knockdown within the ventrolateral @entity550 and unilateral @entity9140 knockdown accompanied by lesions of the contralateral amygdala impede goal-directed response selection, implicating @entity9140 -expressing @entity550 projection neurons in selecting actions based on their consequences. The @entity4149 receptor kinase B agonist @entity21537 rescues action selection and increases dendritic spine density on excitatory neurons in the @entity550 . @entity22636 inhibition also rescues goal-directed response strategies, linking neural remodeling with outcome-based decision making. Finally, DREADD-mediated @entity550 inhibition weakens new action-outcome memory. CONCLUSIONS: Activity-dependent and @entity9140 -dependent neuroplasticity within the @entity550 coordinate outcome-based decision making through interactions with the amygdala. These interactions brake reward-seeking habits, a putative factor in multiple psychopathologies.
