Basal Ganglia Circuit Mechanisms in Cognitive Learning.

The nucleus accumbens (NAc), the ventral part of the striatum, plays a critical role in motivation, learning, and cognition in the basal ganglia circuit. Outputs of the NAc are transmitted through two parallel direct and indirect pathways. We have developed a reversible neurotransmission blocking (RNB) technique, in which neurotransmission of each pathway in the NAc is selectively blocked by specific expression of a transmission-blocking tetanus toxin (D-RNB or I-RNB). In visual cue and reversal tasks in the cross-maze, the NAc direct pathway was critical for learning acquisition. In contrast, the NAc indirect pathway was essential not only for learning flexibility, but also for subsequent acquisition of a new strategy. In place discrimination and serial reversal learning tasks in the IntelliCage, we showed that the NAc indirect pathway controls behavioral flexibility by suppressing the influence of previously correct behavioral strategies during the reversal stage. These basal ganglia circuit mechanisms provide new insight into pathophysiologies associated with compulsive behaviors, including addiction and obesity.