δ-opioid and dopaminergic processes in accumbens shell modulate the cholinergic control of predictive learning and choice.
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.
Behavioural Neuroscience Laboratory, Brain and Mind Research Institute, The University of Sydney, New South Wales 2006, Australia, and Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Queensland 4072, Australia.
Vincent
V
Laurent
Jesus
J
Bertran-Gonzalez
Billy C
BC
Chieng
Bernard W
BW
Balleine
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002755:Choice Behavior / Q000502:physiology*; D003214:Conditioning, Classical; D005455:Fluorescent Antibody Technique; D007395:Interneurons / Q000502:physiology*; D007858:Learning / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018377:Neurotransmitter Agents / Q000378:metabolism; D009714:Nucleus Accumbens / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D020318:Rats, Long-Evans; D011954:Receptors, Dopamine / Q000378:metabolism; D017465:Receptors, Opioid, delta / Q000378:metabolism*
D018377:Neurotransmitter Agents; D011954:Receptors, Dopamine; D017465:Receptors, Opioid, delta; D000109:Acetylcholine
choice; dopamine receptor; goal-directed action; muscarinic acetylcholine receptor M4; nucleus accumbens shell; δ-opioid receptor