Mechanisms and Functions of Brain- Body- Environment Interactions in C. elegans

Introduction

Recent large-scale neuronal activity recordings in awake, behaving animals revealed a new, unexpected neuroscientific principle: widespread neuronal activity patterns across the brain encode parameters of movement. Surprisingly, these brain-wide behavior representations even extend to areas that are implicated in the processing of sensory information (e.g., the visual cortex in mice).

Observations

Thus, a large fraction of the brain's activity seems to be dedicated to representing the animal's current, ongoing behavior. These observations have been made across the animal kingdom, including worms, flies, and mammals, suggesting a universal principle; however, the underlying mechanisms and functions remain unknown.

Research Approach

In this proposal, we take advantage of the tractable model organism C. elegans to tackle this problem, combining brain-wide single-cell resolution Ca2+-imaging in freely behaving animals with genetic circuit manipulation tools.

Theoretical Framework

It was previously recognized that the brain operates in a closed loop, actively sensing its body and its environment and making predictions of movement outcomes to optimally control behavior. Here, we propose to reconcile these long-standing concepts with the new observations of brain-wide behavior representations.

Core Hypothesis

Our core hypothesis is that sensory to motor transformation is a distributed process incorporating multiple functions like:

1. Gain-control
2. Re-afference prediction
3. Predictive processing

Team Expertise

Our team is at the forefront of scientific innovation and discoveries in this field, and we are thereby making substantial contributions to this currently ongoing paradigm shift in our understanding of how the brain operates.

Unique Opportunity

Studying these phenomena in worms offers a unique and timely opportunity to rapidly uncover the universal functions of brain-wide behavioral representations. We therefore aim to make fundamental predictions and to formulate new working hypotheses for similar studies in larger model organisms with more complex brains.