PT  - JOURNAL ARTICLE
AU  - Vincent Laurent
AU  - Jesus Bertran-Gonzalez
AU  - Billy C. Chieng
AU  - Bernard W. Balleine
TI  - δ-Opioid and Dopaminergic Processes in Accumbens Shell Modulate the Cholinergic Control of Predictive Learning and Choice
AID  - 10.1523/JNEUROSCI.4592-13.2014
DP  - 2014 Jan 22
TA  - The Journal of Neuroscience
PG  - 1358--1369
VI  - 34
IP  - 4
4099  - http://www.jneurosci.org/content/34/4/1358.short
4100  - http://www.jneurosci.org/content/34/4/1358.full
SO  - J. Neurosci.2014 Jan 22; 34
AB  - Decision-making depends on the ability to extract predictive information from the environment to guide future actions. Outcome-specific Pavlovian-instrumental transfer (PIT) provides an animal model of this process in which a stimulus predicting a particular outcome biases choice toward actions earning that outcome. Recent evidence suggests that cellular adaptations of δ-opioid receptors (DORs) on cholinergic interneurons (CINs) in the nucleus accumbens shell (NAc-S) are necessary for PIT. Here we found that modulation of DORs in CINs critically influences D1-receptor (D1R)-expressing projection neurons in the NAc-S to promote PIT. First, we assessed PIT-induced changes in signaling processes in dopamine D1- and D2-receptor-expressing neurons using drd2-eGFP mice, and found that PIT-related signaling was restricted to non-D2R-eGFP-expressing neurons, suggesting major involvement of D1R-neurons. Next we confirmed the role of D1Rs pharmacologically: the D1R antagonist SCH-23390, but not the D2R antagonist raclopride, infused into the NAc-S abolished PIT in rats, an effect that depended on DOR activity. Moreover, asymmetrical infusion of SCH-23390 and the DOR antagonist naltrindole into the NAc-S also abolished PIT. DOR agonists were found to sensitize the firing responses of CINs in brain slices prepared immediately after the PIT test. We confirmed the opioid-acetylcholinergic influence over D1R-neurons by selectively blocking muscarinic M4 receptors in the NAc-S, which tightly regulate the activity of D1Rs, a treatment that rescued the deficit in PIT induced by naltrindole. We describe a model of NAc-S function in which DORs modulate CINs to influence both D1R-neurons and stimulus-guided choice between goal-directed actions.