Cerebellar involvement in working memory and decision-making

Abstract

To make decisions, we often draw on information that we saw or heard a few seconds ago. How do we manage to retain that information, analyze it, and convert it into a decision? This ability is enabled by our ``working memory,'' which is considered a hallmark of animal cognition. When working memory is intact, we can incorporate recent environmental and internal cues into our decisions; conversely, impairments of working memory are key features of many cognitive disorders in humans. The brain mechanisms underlying this form of dynamic short-term memory remain poorly understood. Nevertheless, previous research has established powerful frameworks for the study of working memory in decision-making, and numerous brain regions are known to play specific roles in this process.

The cerebellum is a brain structure found in all vertebrates that engages in extensive communication with most of the brain. Many lines of evidence suggest that cerebellar neural activity may support working memory. However, despite an abundance of knowledge on its structure and function in other domains, cerebellar roles in working memory have scarcely been studied at the level of neural circuits. One subregion, the lateral posterior cerebellum, is likely to support working memory: it exhibits strong anatomical, functional, and evolutionary relationships with other brain regions known to support working memory, and it is clinically associated with working memory function.

In this dissertation I present a set of experiments aimed at elucidating neural circuit-level cerebellar roles in working memory. I first establish a new behavioral paradigm in which mice accumulate somatosensory evidence in working memory to guide decisions. I perform reversible disruptions of cerebellar neural activity during evidence accumulation and demonstrate through behavioral modeling that they lead to impairments in working memory function. Additionally, by imaging neural activity in populations of cerebellar Purkinje cells during behavior, I demonstrate that they dynamically encode evidence, choice, and error-related information that may be used to support working memory. Together, these results reveal a previously unknown involvement of the lateral posterior cerebellum in encoding and stabilizing working memory contents during decision-making.