Saturday, May 4, 2024
5/4/2024
Cognitive deficits in schizophrenia and bipolar disorder are associated with altered cerebellar activity and this altered activity is thought to play a causal role in the cognitive deficits observed in these disorders. However, the neural mechanisms underlying cerebellar contributions to intact and impaired cognition have not been fully elucidated. We will address this gap in knowledge by examining the neural mechanisms underlying cerebellar communication with forebrain systems during interval timing – a cognitive task requiring attention, working memory, and precise response timing. The primary emphasis of the previous research on the role of the cerebellum in interval timing has been on the ‘ascending’ cerebello-thamo-frontal cortical pathway. However, the medial frontal cortex also projects back to the cerebellum via the pontine nucleus. This ‘descending’ pathway consists of the medial frontal cortical projection to the rostral pontine nucleus and its mossy fiber projection to the cerebellum. A major goal of the current project is to determine the role(s) of the descending pathway in interval timing. The descending pathway could plausibly modulate cerebellar activity with ramping activity or a tonic increase in activity. We hypothesize that both tonic and ramping activity from the descending pathway modulates activity in the cerebellum by increasing the overall firing rate and precision of ramping, respectively. We also hypothesize that sensory information from the start cues in interval timing combines with information from the medial frontal cortex to support cue-specific and interval-specific ramping of cerebellar output. We will test these hypotheses in two aims that examine the pathways for cue information (Aim 1) and mFC timing information (Aim 2) using optogenetics and electrophysiology in rats during performance of a dual- interval timing task. A broad impact of this project is that we will be able to establish whether there are common mechanisms for cerebellar organization and function in motor learning and cognition. The current proposal is a basic research project, but the findings may have important implications for translational research on the role of the cerebellum in schizophrenia and bipolar disorder. Studies of schizophrenia and bipolar disorder have generally focused on how altered cerebellar function affects frontal cortical function, but it is plausible that the altered activity originates in the cortex (or in both areas) and affects the cerebellum via the descending frontal cortical-pontine-cerebellum pathway. The findings of our project could form the foundation for translational research into how descending pathway abnormalities relate to cognitive symptoms in schizophrenia and bipolar disorder.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
