Visualizing deep hippocampus neuronal functional activity in vivo using ultra-thin 2-photon endoscopes

Host laboratory and collaborators

Hervé Rigneault / Fresnel Institute /

Rosa Cossart / INMED /

Scientific background

Most brain functions are encoded by specific neuronal activity patterns with characteristic temporal and spatial dynamics. This proposal will focus on the hippocampus, a brain region supporting memory and encoding spatial and temporal information. Hippocampal dynamics result from the interaction between self-organized internal dynamics and various external inputs from the environment. We want to know how development shapes the final functional organization of adult hippocampal networks: do they self-organize through the interaction of active neurons or do they emerge in reference to a blueprint determined by early developmental programs like genetic factors? To image and record the deep hippocampus neuron activity we have been developing an ultra-thin flexible endoscope that is able to perform 2-photon imaging deep in the brain at depth location that are inaccessible using 2-photon microscopy.

PhD Objectives

The goal of this PhD project is to develop and use 2-photon ultra-thin lensless endoscopy to image in vivo the activity patterns of hippocampus regions CA3 and CA1 in mice brain, in a minimally invasive manner and in varying environmental contexts. This will allow for the study of spatio-temporal information transfer from the deep CA3 region to the more organized CA1 region. This first major biological question is proving the drive for a technological development that will obviously pave the way to image deep brain structures in living animal models.

Proposed approach

Experimental: In this PhD project we will first consist in finalizing the development of the ultra-thin lensless endoscope and use it to record neural activity either in CA1 or CA3 in freely moving mice or simultaneously in CA1 and CA3 in mice running on a treadmill. In this second case, recording in CA1 will be performed using 2-photon microscopy while CA3 activity will be performed using the ultra-thin lensless endoscope technology. The PhD project specifically aims at determining how CA1 cell assemblies and sequences are shaped by the spatio-temporal patterning of activity in CA3 and how these patterns hold in 2D environments.

PhD student’s expected profile

We are seeking for a motivated and skilled applicant with a solid background in optical engineering and a strong interest to apply innovative photonic instruments to the field of neurosciences.