Vascular Interactions and Remodeling during Gestation and its Impact on Neuronal functions

Introduction

An intricate network of blood vessels perfuses the brain to support neural cells and carry signaling molecules from the periphery. It is mainly considered a rigid “transportation network” rather than a dynamic and plastic “information network” integrated to neurons and glia. This proposal revisits this concept and aims to define the nature of vascular remodeling in healthy brains (i) and which remodeling mechanisms play a role in shaping plastic neuronal functions (ii).

Project Overview

The project VIRGINS explores this in the context of the neurophysiological adaptations occurring during and after pregnancy. There, sexual hormones promote neuronal plasticity, which tunes the cerebral control of energy balance and drives the emergence of parental behaviors.

Findings

Using our unbiased whole-brain vascular mapping technique TubeMap, we found that in pregnant mouse brains, vascular territories of regions controlling energy homeostasis and hormonal states are remodeled:

• The Arcuate nucleus
• The PeriVentricular nucleus
• The ParaVentricular nucleus
• The DorsoMedial nucleus of the Hypothalamus

We also found remodeling of blood vessels in brain regions processing pup calls:

• The auditory cortex
• The prefrontal cortex
• The hippocampus
• Subcortical relays

The regional specificity of this vascular plasticity suggests precise and complex regulatory mechanisms and a role in shaping neuronal functions in the pregnant state.

Methodology

To link structural, functional, and molecular changes in the neurovascular unit during gestation, we will use:

1. Light sheet brain mapping
2. Neurovascular (fast ultrasounds)
3. 2-photon imaging with transcriptomics
4. Molecular and behavioral tools

These methods will help us determine:

1. The nature of whole brain vascular plasticity during pregnancy
2. Its mechanisms and impact on the control of energy homeostasis
3. Its role in the tuning of the auditory system to infant calls

Conclusion

This project will transform our view on the capacity of the NeuroVascular Unit to sculpt neuronal computation and behaviors.