XXXX 's Actions in Primate Prefrontal Cortex: Challenges for Treating @entity73 .

@entity3264 @entity1246 @entity935 @entity73 @entity8614 @entity161 @entity1633
The prefrontal cortex (PFC) elaborates and differentiates in primates, and there is a corresponding elaboration in cortical @entity935 (DA). DA cells that fire to both aversive and rewarding stimuli likely project to the dorsolateral PFC (dlPFC), signaling a salient event. Since 1979, we have known that DA has an essential influence on dlPFC working memory functions. DA has differing effects via D1 (D1R) versus @entity1633 ( @entity1633 ) families. D1R are concentrated on dendritic spines, and D1/5R stimulation produces an inverted U-shaped dose response on visuospatial working memory performance and Delay cell firing, the neurons that generate representations of visual space. Optimal levels of D1R stimulation gate out "noise," whereas higher levels, e.g., during stress, suppress Delay cell firing. These effects likely involve hyperpolarization-activated @entity8614 -gated channel opening, activation of @entity1246 interneurons, and reduced @entity3264 release. Dysregulation of D1R has been related to @entity73 in @entity161 , and there is a need for new, lower-affinity D1R agonists that may better mimic endogenous DA to enhance mental representations and improve cognition. In contrast to D1R, @entity1633 are primarily localized on layer V pyramidal cell dendrites, and D2/3R stimulation speeds and magnifies the firing of Response cells, including Response Feedback cells. Altered firing of Feedback neurons may relate to positive symptoms in @entity161 . Emerging research suggests that DA may have similar effects in the ventrolateral PFC and frontal eye fields. Research on the orbital PFC in monkeys is just beginning and could be a key area for future discoveries.
