Dopamine receptors mediate strategy abandoning via modulation of a specific prelimbic cortex–nucleus accumbens pathway in mice

Qiaoling Cui, Qian Li, Hongyan Geng, Lei Chen, Nancy Y. Ip, Ya Ke*, Wing Ho Yung

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


The ability to abandon old strategies and adopt new ones is essential for survival in a constantly changing environment. While previous studies suggest the importance of the prefrontal cortex and some subcortical areas in the generation of strategy-switching flexibility, the fine neural circuitry and receptor mechanisms involved are not fully understood. In this study, we showed that optogenetic excitation and inhibition of the prelimbic cortex–nucleus accumbens (NAc) pathway in the mouse respectively enhances and suppresses strategy-switching ability in a cross-modal spatial-egocentric task. This ability is dependent on an intact dopaminergic tone in the NAc, as local dopamine denervation impaired the performance of the animal in the switching of tasks. In addition, based on a brain-slice preparation obtained from Drd2-EGFP BAC transgenic mice, we demonstrated direct innervation of D2 receptor-expressing medium spiny neurons (D2-MSNs) in the NAc by prelimbic cortical neurons, which is under the regulation by presynaptic dopamine receptors. While presynaptic D1-type receptor activation enhances the glutamatergic transmission from the prelimbic cortex to D2-MSNs, D2-type receptor activation suppresses this synaptic connection. Furthermore, manipulation of this pathway by optogenetic activation or administration of a D1-type agonist or a D2-type antagonist could restore impaired task-switching flexibility in mice with local NAc dopamine depletion; this restoration is consistent with the effects of knocking down the expression of specific dopamine receptors in the pathway. Our results point to a critical role of a specific prelimbic cortex–NAc subpathway in mediating strategy abandoning, allowing the switching from one strategy to another in problem solving.

Original languageEnglish (US)
Pages (from-to)E4890-E4899
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number21
StatePublished - May 22 2018
Externally publishedYes


  • Task-switching
  • dopamine receptors
  • nucleus accumbens
  • prelimbic cortex
  • strategy abandoning

ASJC Scopus subject areas

  • General


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