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


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.

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Figure 1: Local field potential responses in the NAcc evoked by PFC and hippocampus stimulation.
Figure 2: Graphs illustrating the range of the intracranial placements around the targeted regions in electrophysiological and behavioral experiments.
Figure 3: Selective modulation of hippocampus- and PFC-evoked field potential responses in the NAcc by local infusion of D1 and D2 agonists and antagonists.
Figure 4: Selective modulation of hippocampus- and PFC-evoked responses in the NAcc by activation and inactivation of the ventral pallidum and PPTg.
Figure 5: The effects of D1 and D2 antagonists on modulation of hippocampus (HPC)- and PFC-evoked responses in the NAcc by activation and inactivation of the ventral pallidum (VP) and PPTg.
Figure 6: Analyses of pre- versus postsynaptic DA modulation of hippocampus- and PFC-evoked responses.
Figure 7: The effects of hippocampus-NAcc and PFC-NAcc functional disconnection by unilateral inactivation of the hippocampus or PFC combined with contralateral D1 antagonist or D2 agonist infusion into the NAcc on performance in the plus maze tasks.


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We thank N. Macmurdo and C. Smolak for technical assistance, B. Lowry for data acquisition software and A. West and M. Takita for suggestions on reverse microdialysis technique. This work was supported by US National Institute of Mental Health MH57440 (A.A.G.) and a National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Award (Y.G.). Y.G. is a NARSAD Essel Investigator.

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Correspondence to Yukiori Goto.

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Supplementary information

Supplementary Fig. 1

Schematic diagrams illustrating how PFC and HPC information processing in the NAcc is modulated by tonic and phasic DA release. (PDF 287 kb)

Supplementary Note (PDF 74 kb)

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Goto, Y., Grace, A. Dopaminergic modulation of limbic and cortical drive of nucleus accumbens in goal-directed behavior. Nat Neurosci 8, 805–812 (2005).

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