Comparative roles of caudate and putamen in the serial order of behavior: Effects of striatal glutamate receptor blockade on variable versus fixed spatial self-ordered sequencing in marmosets

Abstract

Self-ordered sequencing is an important executive function involving planning and executing a series of steps to achieve goal-directed outcomes. Lateral frontal cortex is implicated in this behavior, but downstream striatal outputs remain relatively unexplored. We trained marmosets on a three-stimulus self-ordered spatial sequencing task using a touch-sensitive screen to explore the role of caudate nucleus and putamen in random and fixed response arrays. By transiently blocking glutamatergic inputs to these regions, using intra-striatal CNQX microinfusions, we demonstrate that caudate and putamen are both required for, but contribute differently to, flexible and fixed sequencing. CNQX into either caudate or putamen impaired variable array accuracy, and infusions into both simultaneously elicited greater impairment. We demonstrated that continuous perseverative errors in variable array were caused by putamen infusions, likely due to interference with the putamen's established role in monitoring motor feedback. Caudate infusions, however, did not affect continuous errors, but did cause an upward trend in recurrent perseveration, possibly reflecting interference with the caudate's established role in spatial working memory and goal-directed planning. In contrast to variable array performance, whilst both caudate and putamen both impaired fixed array responding, the combined effects were not additive, suggesting possible competing roles. Infusions into either region individually, but not simultaneously, led to continuous perseveration. Recurrent perseveration in fixed arrays was caused by putamen, but not caudate, infusions. These results are consistent overall with a role of caudate in planning and flexible responding, and the putamen in more rigid habitual or automatic responding.

Significance Statement This investigation employing local intra-striatal infusions into caudate nucleus and/or putamen of the New World marmoset reveals important roles for these regions in variable and fixed spatial self-ordered sequencing. Here, we directly implicate subcortical output regions of the lateral prefrontal cortex in self-ordered sequencing behavior. The ability to self-order sequences, as well as more broadly to plan, organize information, and respond flexibly, is impaired in many neurological diseases and psychiatric disorders. By understanding the basic neural circuitry underlying these cognitive abilities, we may better understand how to rectify them in people with deficits across a plethora of disorders.