Dopaminergic modulation of limbic and cortical drive of nucleus accumbens in goal-directed behavior

Abstract

Goal-directed behavior is believed to involve interactions of prefrontal cortical and limbic inputs in the nucleus accumbens (NAcc), and their modulation by mesolimbic dopamine (DA) seems to be of primary importance in NAcc function. Using in vivo electrophysiological recordings simultaneously with DA system manipulation in rats, we show that tonic and phasic DA release selectively modulates hippocampal and prefrontal cortical inputs through D1 and D2 receptors, respectively. In addition, we also found that D1 activation and D2 inactivation in the NAcc produced behaviorally selective effects (learning versus set shifting of response strategy) that correspond to specific afferents. These results suggest that the dynamics of DA release regulate the balance between limbic and cortical drive through activation and inactivation of DA receptor subtypes in the accumbens, and this regulates goal-directed behavior.

L-DOPA Disrupts Activity in the Nucleus Accumbens during Reversal Learning in Parkinson's Disease

“…Our finding concurs with the observation that the effect of L-DOPA stems from its ability to elevate DA in the striatum (Hornykiewicz, 1974;Carey et al, 1995) and suggests that at least some 'frontal-like' deficits in PD reflect disruption of frontal input to the striatum (Goto and Grace, 2005) or alternatively, striatal outflow to the PFC (Owen et al, 1998;Dagher et al, 2001). The present lack of cortical modulation of reversal-related activity apparently contradicts results from previous imaging studies in PD, which have revealed cortical changes (Cools et al, 2002b;Mattay et al, 2002;Lewis et al, 2003;Monchi et al, 2004).…”

“…In the OFF state, patients demonstrated NAc activity during the final reversal errors that preceded behavioral adaptation. L-DOPA disrupted this NAc activity, consistent with work with experimental animals (Goto and Grace, 2005). These findings support the suggestion that DA interacts with the NAc to bias reversal learning and demonstrate the utility of early PD, with differentially depleted neural systems, as a model for exploring the role of DA in normal cognitive function.…”

“…The L-DOPA-induced disruption of NAc activity parallels observations from Goto and Grace (2005). These authors revealed that increases in tonic DA release in the NAc and administration of a DA (D2) receptor agonist in the NAc disrupted PFC-evoked responses in the NAc and impaired behavioral reversal learning in rats.…”

“…Our finding of normal reversal learning coupled with disrupted NAc activity in patients ON L-DOPA suggests that switching in the present paradigm did not depend on supra-threshold NAc activity. Reversal learning most likely does depend on supra-threshold NAc activity in single-reversal tasks, because tonic DA release, DA receptor activation and damage in the NAc have been shown to disrupt such one-time reversal learning (Smith et al, 1999;Schoenbaum and Setlow, 2003;Goto and Grace, 2005;Divac et al, 1967;Taghzouti et al, 1985;Annett et al, 1989;Stern and Passingham, 1995). However, the extensive practice in the present task likely enabled participants (ON as well as OFF L-DOPA) to rely on different (cortical) neural mechanisms, helping them to perform well despite accumbens abnormality.…”

Anatomy of a decision: Striato-orbitofrontal interactions in reinforcement learning, decision making, and reversal.

“…GPe ϭ external segment of the globus pallidus. Goto & Grace, 2005). Thus, smaller decreases in DA firing may be sufficient to functionally affect D 2 receptors, which drives no-go learning in our model.…”