Conférence mensuelle – Valentina Emiliani

Toward circuit optogenetics

Lieu : Centre Broca Nouvelle-Aquitaine.

Valentina Emiliani
Wavefront-engineering microscopy group
Photonics Department
Vision Institut
UMRS 968 Inserm / UPMC / CNRS / CHNO des Quinze-Vingts – Paris

Invitée par : Association NBA / Bordeaux Neurocampus

Abstract

Optogenetics neuronal targeting combined with single-photon wide-field illumination has already proved its enormous potential in neuroscience, enabling the optical control of entire neuronal network and disentangling their role in the control of specific behaviors. However, establishing how a single or a sub-set of neurons controls a specific behavior, or how functionally identical neurons are connected in a particular task, or yet how behaviors can be modified in real-time by the complex wiring diagram of neuronal connections requires more sophisticated approaches enabling to drive neuronal circuits activity with single cell precision and millisecond temporal resolution. This has motivated on one side the development of flexible optical methods for two-photon (2P) optogenetic activation using either, or a hybrid of two approaches: scanning and parallel illumination. On the other side, it has stimulated the engineering of new opsin with modified spectral characteristics, channel kinetics and spatial distribution of expression, offering the necessary flexibility of choosing the appropriate opsin for each application. The need for optical manipulation of multiple targets with millisecond temporal resolution has imposed 3D parallel holographic illumination as the technique of choice for optical control of neuronal circuits organized in 3D. Today 3D parallel illumination exists in different complementary variants, which privilege either simplicity or temporal precision or axial resolution. In parallel, the possibility to reach hundreds of targets in 3D volumes has prompted the development of low-repetition rate amplified lasers source enabling higher total exit power while keeping low average power for stimulating each cell.

All together those progresses have now brought the field of optogenetics into a new phase that we can name “circuit optogenetics”, where neural circuits distributed between different brain areas can be optically interrogated and controlled with millisecond temporal precision and single-cell resolution. Here, I will present the main achievements of my group in this field and discuss the future needs that will make it possible to enlarge even more the use of optogenetics for brain circuits manipulation.

Selected publications

Alexis Picot, Soledad Dominguez, Chang Liu, I-Wen Chen, Dimitrii Tanese, Emiliano Ronzitti, Pascal Berto, Eirini Papagiakoumou, Dan Oron^, Gilles Tessier, Benoît C. Forget, and Valentina Emiliani, Temperature rise under two-photon optogenetics brain stimulation, Cell Report (2018) in press

O. Shemesh, D. Tanese, V. Zampini, L. Changyang, P. Kiryln, E. Ronzitti, E. Papagiakoumou, E.S. Boyden, V. Emiliani, Temporally precise single-cell resolution optogenetics, Nature Neuroscience (2017) 20,  1796–1806

V. Szabo, C. Ventalon, V. De Sars, J. Bradley, and V. Emiliani, Spatially selective holographic photoactivation and functional fluorescence imaging in freely behaving mice with a fiberscope, Neuron 84, 1157-1169 (2014).

E. Papagiakoumou, A. Begue, B. Leshem, O. Schwartz, B. M. Stell, J. Bradley, D. Oron, and V. Emiliani, Functional patterned multiphoton excitation deep inside scattering tissue, Nature Photonics 7, 274-278 (2013).

E. Papagiakoumou, F. Anselmi, A. Begue, V. de Sars, J. Gluckstad, E. Y. Isacoff, and V. Emiliani, Scanless two-photon excitation of channelrhodopsin-2, Nature Methods 7, 848-854 (2010).