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D1 and D2 medium spiny neurons in the nucleus accumbens core have distinct and valence-independent roles in learning

2023; Cell Press; Volume: 112; Issue: 5 Linguagem: Inglês

10.1016/j.neuron.2023.11.023

1097-4199

Jennifer E. Zachry, Munir Gunes Kutlu, Hye Jean Yoon, Michael Z. Leonard, Maxime Chevée, Dev D. Patel, Anthony Gaidici, Veronika Kondev, Kimberly C. Thibeault, Rishik Bethi, Jennifer Tat, Patrick R. Melugin, Atagun U. Isiktas, Max E. Joffe, Denise J. Cai, P. Jeffrey Conn, Brad A. Grueter, Erin S. Calipari,

Receptor Mechanisms and Signaling

At the core of value-based learning is the nucleus accumbens (NAc). D1- and D2-receptor-containing medium spiny neurons (MSNs) in the NAc core are hypothesized to have opposing valence-based roles in behavior. Using optical imaging and manipulation approaches in mice, we show that neither D1 nor D2 MSNs signal valence. D1 MSN responses were evoked by stimuli regardless of valence or contingency. D2 MSNs were evoked by both cues and outcomes, were dynamically changed with learning, and tracked valence-free prediction error at the population and individual neuron level. Finally, D2 MSN responses to cues were necessary for associative learning. Thus, D1 and D2 MSNs work in tandem, rather than in opposition, by signaling specific properties of stimuli to control learning.