Neuroscience

Dopamine receptor D2

Central nervous system

Biology

Indirect pathway of movement

Psychology

Basal ganglia

Nucleus accumbens

Globus pallidus

Ventral pallidum

Striatum

Dopamine

Reinforcement

Medium spiny neuron

Optogenetics

Social psychology

Cell Reports

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.

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