SY35-2 * DORSAL STRIATAL INDIRECT PATHWAY REGULATES THE PERFORMANCE OF AUDITORY CONDITIONAL DISCRIMINATION

Abstract

The dorsal striatum, which contains the dorsolateral striatum (DLS) and dorsomedial striatum (DMS), is known to be involved in the performance of discrimination learning. The dorsal striatum regulates the basal ganglia circuitry through direct and indirect pathways. However the mechanism by which the striatopallidal pathway regulates the learning processes of discriminative actions remains unclear. To induce selective elimination of the striatopallidal pathway by injecting the recombinant immunotoxin into the DLS or DMS, we used transgenic rats that expressed human interleukin-2 receptor alpha-subunit under the control of dopamine D2 receptor gene promoter. Intrastriatal immunotoxin treatment induced a selective elimination of the striatopallidal neurons while persisting normally the number of other striatal neuronal types. Ablation of the DLS- or DMS-derived striatopallidal pathway transiently impaired the performance of conditional discrimination, showing a marked reduction in the selection accuracy of learned motor responses. In addition, the probability of perseverative errors was significantly increased in the animals lacking the striatopallidal pathway from the DMS, but not from the DLS. Although there is a distinct role in modulating perseverative behavior between the DLS- and DMS-derived striatopallidal pathways, these two pathways are necessary for controlling the accuracy of response selection.