Delineating Convergent and Divergent Cortico-Cerebellar pathways in motor Control

Introduction

The CODI-MAP aims to address a fundamental question: How do the cerebral cortex and cerebellum cooperate to generate and regulate movements? Despite their pivotal contribution to motor control, the complex nature of cortico-cerebellar interaction remains a mystery.

Research Background

Our recent work has demonstrated a significant interdependency between the cortical and cerebellar activities. However, the precise architecture and computational strategy that cortico-cerebellar circuits employ to generate and maintain task-specific information is unknown.

Objectives

Here, I propose to comprehensively address the following aspects:

1. The detailed reciprocal connectivity of the cortico-cerebellar circuits.
2. Their functional interaction during goal-directed voluntary movements.
3. Their contribution to sensorimotor learning.

Central Hypothesis

Our central hypothesis is that the cortico-cerebellar circuits form complex networks characterized by both extensive convergence and divergence. This configuration provides a spectrum of task-related functional modules for sensorimotor control and learning. By engaging specific functional modules, the cortico-cerebellar networks achieve the required spatiotemporal precision for directing movements.

Methodology

We will first systematically dissect the anatomical and molecular features of the cortico-cerebellar pathways using a suite of sophisticated combinatorial viral-genetic strategies. Next, we will identify and manipulate the functional circuits that control forelimb movements using novel multi-regional electrophysiological and optical methods. Finally, we will combine in silico simulation with dual-regional optical recording and manipulation to uncover the plastic changes within cortico-cerebellar circuits during learning.

Expected Outcomes

The outcome of this project has the potential to challenge the conventional perspective that considers cortex and cerebellum as distinct computational entities. It proposes a multi-regional integrative circuitry, thereby unveiling fundamental principles of how the brain generates action.