Abstract
Dopamine (DA) level in the nucleus accumbens (NAc) is critical for reward and aversion encoding. DA released from the ventral mesencephalon (VM) DAergic neurons increases the excitability of VM-projecting D1-dopamine receptor-expressing medium spiny neurons (D1-MSNs) in the NAc to enhance DA release and augment rewards. However, how such a DA positive feedback loop is regulated to maintain DA homeostasis and reward-aversion balance remains elusive. Here we report that the ventral pallidum (VP) projection of NAc D1-MSNs (D1NAc-VP) is inhibited by rewarding stimuli and activated by aversive stimuli. In contrast to the VM projection of D1-MSN (D1NAc-VM), activation of D1NAc-VP projection induces aversion, but not reward. D1NAc-VP MSNs are distinct from the D1NAc-VM MSNs, which exhibit conventional functions of D1-MSNs. Activation of D1NAc-VP projection stimulates VM GABAergic transmission, inhibits VM DAergic neurons, and reduces DA release into the NAc. Thus, D1NAc-VP and D1NAc-VM MSNs cooperatively control NAc dopamine balance and reward-aversion states.
Highlights
Emotional valence, the positive or negative internal state of an animal,[1] is fundamental for motivated behavior and reinforcement learning.[2]
We show that activation of ventral mesencephalon (VM)- and ventral pallidum (VP)-projections of nucleus accumbens (NAc) D1-medium spiny neurons (MSNs) (D1NAc-VM and D1NAc-VP pathways) is elicited by stimuli of different valences and produces opposing behavioral responses
Negative stimulus induces activation of D1NAc-VP projection and concurrent suppression of D1NAc-VM projection, while positive stimulus suppresses D1NAc-VP projection and concurrently activates D1NAc-VM projection To explore the potential roles of projections of NAc D1-MSNs to VM and VP, we first examined their responses to stimuli of positive and negative valences
Summary
The positive (rewarding) or negative (aversive) internal state of an animal,[1] is fundamental for motivated behavior and reinforcement learning.[2]. The prevailing model posits that the activation of D1-MSNs is rewarding and activation of D2-MSNs is aversive.[11,12] Optogenetic activation of NAc D1-MSNs enhances cocaine-induced conditioned place preference (CPP), whereas optogenetic activation of D2-MSNs suppresses it.[13] Chemogenetic inhibition of NAc D2MSNs augments cocaine seeking.[14] It has been demonstrated that. DA release in the NAc activates both D1- and D2-dopamine receptors, and increases cAMP/PKA activity in D1-MSNs and inhibits cAMP/PKA activity in D2-MSNs.[15,16] DA binding to. D1- and D2-receptors enhances excitability of D1-MSNs and decreases the excitability of D2-MSNs through the regulation of cAMP/PKA signaling.[15,17] It was well known that activation of D1 receptor and inactivation of D2 receptors in the NAc produces opposing behavioral effects.[18] DA release induced activation of
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