Distinct role of nucleus accumbens D2-MSN projections to ventral pallidum in different phases of motivated behavior

• Published in: Cell reports (Cambridge) Vol. 38; no. 7; p. 110380
• Main Authors: Soares-Cunha, Carina, Domingues, Ana Verónica, Correia, Raquel, Coimbra, Bárbara, Vieitas-Gaspar, Natacha, de Vasconcelos, Nivaldo A.P., Pinto, Luísa, Sousa, Nuno, Rodrigues, Ana João
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15-02-2022; Cell Press
• Subjects: Animals; Basal Forebrain - physiology; Behavior, Animal - physiology; Cues; Feeding Behavior; Male; medium spiny neurons; Motivation; Neurons - physiology; nucleus accumbens; Nucleus Accumbens - physiology; Optogenetics; Rats; Rats, Wistar; Receptors, Dopamine D2 - metabolism; Reward; striatum; ventral pallidum; reward; striatum; motivation; ventral pallidum; medium spiny neurons; nucleus accumbens; D2
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2022.110380

The nucleus accumbens (NAc) is a key region in motivated behaviors. NAc medium spiny neurons (MSNs) are divided into those expressing dopamine receptor D1 or D2. Classically, D1- and D2-MSNs have been described as having opposing roles in reinforcement, but recent evidence suggests a more complex role for D2-MSNs. Here, we show that optogenetic modulation of D2-MSN to ventral pallidum (VP) projections during different stages of motivated behavior has contrasting effects in motivation. Activation of D2-MSN-VP projections during a reward-predicting cue results in increased motivational drive, whereas activation at reward delivery decreases motivation; optical inhibition triggers the opposite behavioral effect. In addition, in a free-choice instrumental task, animals prefer the lever that originates one pellet in opposition to pellet plus D2-MSN-VP optogenetic activation and vice versa for optogenetic inhibition. In summary, D2-MSN-VP projections play different, and even opposing, roles in distinct phases of motivated behavior.
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•Increased D2-MSN-VP activity during reward-predicting cue enhances motivation•Suppression of D2-MSN-VP activity during reward consumption increases motivation
Soares-Cunha et al. show that optogenetic modulation of nucleus accumbens D2-MSN to ventral pallidum projections during different stages of motivated behavior has contrasting effects in motivation: cue-paired optical activation of D2-MSN-VP inputs increases motivation to work for food, whereas reward-paired activation reduces motivation.