Cerebellar D1DR-expressing neurons modulate the frontal cortex during timing tasks.

Abstract

Converging lines of evidence suggest that the cerebellum plays an integral role in cognitive function through its interactions with association cortices like the medial frontal cortex (MFC). It is unknown precisely how the cerebellum influences the frontal cortex and what type of information is reciprocally relayed between these two regions. A subset of neurons in the cerebellar dentate nuclei, or the homologous lateral cerebellar nuclei (LCN) in rodents, express D1 dopamine receptors (D1DRs) and may play a role in cognitive processes. We investigated how pharmacologically blocking LCN D1DRs influences performance in an interval timing task and impacts neuronal activity in the frontal cortex. Interval timing requires executive processes such as working memory, attention, and planning and is known to rely on both the frontal cortex and cerebellum. In our interval timing task, male rats indicated their estimates of the passage of a period of several seconds by making lever presses for a water reward. We have shown that a cue-evoked burst of low-frequency activity in the MFC initiates ramping activity (i.e., monotonic increases or decreases of firing rate over time) in single MFC neurons. These patterns of activity are associated with successful interval timing performance. Here we explored how blocking right LCN D1DRs with the D1DR antagonist SCH23390 influences timing performance and neural activity in the contralateral (left) MFC. Our results indicate that blocking LCN D1DRs impaired some measures of interval timing performance. Additionally, ramping activity of MFC single units was significantly attenuated. These data provide insight into how catecholamines in the LCN may drive MFC neuronal dynamics to influence cognitive function.