Pathway-specific control of reward learning and its flexibility via selective dopamine receptors in the nucleus accumbens

Satoshi Yawata, Takashi Yamaguchi, Teruko Danjo, Takatoshi Hikida, Shigetada Nakanishi

Research output: Contribution to journalArticlepeer-review

83 Citations (Scopus)

Abstract

In the basal ganglia, inputs from the nucleus accumbens (NAc) are transmitted through both direct and indirect pathways and control reward-based learning. In the NAc, dopamine (DA) serves as a key neurotransmitter, modulating these two parallel pathways. This study explored how reward learning and its flexibility are controlled in a pathway-specific and DA receptor-dependent manner. We used two techniques (i) reversible neurotransmission blocking (RNB), in which transmission of the direct (D-RNB) or the indirect pathway (I-RNB) in the NAc on both sides of the hemispheres was selectively blocked by transmission-blocking tetanus toxin; and (ii) asymmetric RNB, inwhich transmission of the direct (D-aRNB) or the indirect pathway (I-aRNB) was unilaterally blocked by RNB techniques and the intact side of the NAc was infused with DA agonists or antagonists. Reward-based learning was assessed by measuring goal-directed learning ability based on visual cue tasks (VCTs) or response-direction tasks (RDTs). Learning flexibility was then tested by switching from a previously learned VCT to a new VCT or RDT. D-RNB mice and D1 receptor antagonist-treated D-aRNB mice showed severe impairments in learning acquisition but normal flexibility to switch from a previously learned strategy. In contrast, I-RNB mice and D2 receptor agonist-treated I-aRNB mice showed normal learning acquisition but severe impairments not only in the flexibility to the learning switch but also in the subsequent acquisition of learning a new strategy. D1 and D2 receptors thus play distinct but cooperative roles in reward learning and its flexibility in a pathway-specific manner.

Original languageEnglish
Pages (from-to)12764-12769
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number31
DOIs
Publication statusPublished - 31-07-2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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