Activation of prefrontal cortex and striatal regions in rats after shifting between rules in a T-maze.

Prefrontal cortical and striatal areas have been identified by inactivation or lesion studies to be required for behavioral flexibility, including selecting and processing of different types of information. In order to identify these networks activated selectively during the acquisition of new reward contingency rules, rats were trained to discriminate orientations of bars presented in pseudorandom sequence on two video monitors positioned behind the goal sites on a T-maze with return arms. A second group already trained in the visual discrimination task learned to alternate left and right goal arm visits in the same maze while ignoring the visual cues still being presented. In each experimental group, once the rats reached criterion performance, the brains were prepared after a 90-min delay for later processing for c-fos immunohistochemistry. While both groups extinguished a prior strategy and acquired a new rule, they differed by the identity of the strategies and previous learning experience. Among the 28 forebrain areas examined, there were significant increases in the relative density of c-fos immunoreactive cell bodies after learning the second rule in the prefrontal cortex cingulate, the prelimbic and infralimbic areas, the dorsomedial striatum and the core of the nucleus accumbens, the ventral subiculum, and the central nucleus of the amygdala. These largely correspond to structures previously identified in inactivation studies, and their neurons fire synchronously during learning and strategy shifts. The data suggest that this dynamic network may underlie reward-based selection for action-a type of cognitive flexibility.