Optical probing hub neurons in vivo
The coordinated activation of neuronal networks supports adaptive behavior and cognitive functions. A common approach to reduce network complexity is to outline functional motifs or focus on cell subtypes and infer their functional role by selectively modulating them. Targeted cell modulation has proven successful in vitro as it enabled the finding of hub neurons by the host lab. Hub cells coordinate neuronal activity in the developing hippocampus in vitro (Bonifazi et al. Science 2009). Hubs may critically control cortical development; however, it remains unknown whether the same or functionally similar hub cells operate in vivo. This proposal aims at exploring hub function in un-anesthetized mouse pups. This is a technical challenge that can be overcome by the implementation of 3D- all optical dissection of hippocampal circuits in mouse pups. As such, we aim at recruiting a physicist specialized in optics for a project at the crossroads between neuroscience, optics and network science.
Neuroscience; Imaging; optogenetics; hippocampus; development; networks; hub cells
Aim 1: Implementation of all-optical imaging and stimulation in the developing hippocampus in vivo: A custom-made set up based on 2-photon calcium imaging coupled with holographic light patterning has been recently built in the Cossart lab in collaboration with the Emiliani group. The candidate will adapt and optimize the set-up for use in the developing hippocampus.
Aim 2: Finding and stimulating hub neurons: Hub cells will be identified based on functional connectivity mapping and targeted for light stimulation.
Proposed approach (experimental / theoretical / computational)
Experimental (optics/neuroscience): The use of our custom-build 2photon -imaging and -patterned holographic stimulation set-up has been validated in the developing barrel cortex, a cortical region at the surface of the brain displaying anatomically scattered neurons. The developing hippocampus is a double-challenge since: (1) it is a deeper region, not as easily accessible; (2) neurons are densely packed in the pyramidal layer, complexifying single-cell stimulation. The candidate will work on optimizing the light source and employ new soma-targeted opsins for the purpose of the project, in collaboration with the lab of Hervé Rigneault. Hub cells will be identified online as previously described using functional connectivity analysis from single-cell calcium transients.
Computational/theoretical: A program for online analysis of functional connectivity schemes and hub cell detection will be designed by the candidate, in collaboration with the lab of Alain Barrat.
This is a proposal at the crossroads between neuroscience, optics and complex network science. Understanding how brain circuits are organized to support behavior and understanding is the challenge of modern neuroscience. The recent burst of all optical approaches to monitor and manipulate brain circuits is providing a unique opportunity to meet this goal. However, it requires neurobiologists to work in close cooperation with physicists specialized in optics to design custom-made state of the art experimental setups. The project will be carried out in a neuroscience lab but the candidate should have a PhD in optics. The host lab has provided the first experimental demonstration for the existence of hub neurons. Hub neurons is a concept borrowed from graph theory applied to neuroscience in order to understand the functional connectivity schemes emerging in large neuronal networks. This interdisciplinary concept is the focus of the proposal and analysis will be fed by the expertise of Dr. Barrat.