Multi-omics characterization of descending motor circuits in the brainstem

Introduction

The execution of coordinated and adaptive movements is the final manifestation of virtually all brain processes. Altered motor function is hence an associate feature of almost all conditions that affect the nervous system and is highly debilitating. This program will shed new light on the neuronal basis of movements with a focus on the cooperative roles of the brain and the spinal cord for composing and orchestrating multifaceted and adaptive motor behaviors.

Role of Reticulospinal Neurons

Reticulospinal (RS) neurons of the brainstem reticular formation (RF) are pivotal for controlling the most vital movements. They have long been seen as a unified relay of command signals from various integrative centers upstream to most, if not all, “executory” motor circuits downstream.

Diversity and Specialization

Yet, based on recent findings and our ongoing work, we posit that RS neurons rather exhibit a substantial diversity and specialization by inputs and outputs that may support a form of selection and mixing of unitary components of composite motor behaviors.

Research Methodology

Imprinting from the advent of “multi-omics” strategies in the mouse model, we will intersect functional connectomics and single-cell gene expression (the transcriptome) to achieve a most comprehensive characterization of RS neurons’ diversity, specialization, and interactions with their upstream and downstream brain areas.

Investigation Focus

1. We will first investigate the anatomo-functional organization of an already circumscribed subset of RS neurons for orchestrating orienting motor actions.
2. We will in parallel investigate the role and connectivity of other RS neurons.
3. We will provide genetic hallmarks of new functionally-relevant subsets.

Expected Outcomes

Our results will propel forward our understanding of the complex organization of the RF, its role in orchestrating composite movements, and its links with the rest of the brain. They will also provide new genetic hallmarks of RS neurons’ diversity which will be precious handles to ultimately examine and act on specific cell types in post-traumatic contexts.