DONATE MAINS

Laboratory : Photonics Department – Institute de la Vision; 17 rue Moreau 75012, Paris
Advisors : Valentina Emiliani; Emiliano Ronzitti; Eirini Papagiakoumou
Email : valentina.emiliani@inserm.fr; emiliano.ronzitti@inserm.fr; Eirini.papagiakoumou@inserm.fr
Phone : (+33) 1 53 46 26 70; (+33) 1 53 46 27 02

The Emiliani Lab at the Vision Institute in Paris opens a PhD position in 3P microscopy, financed by an ERC Advanced Grant.

Motivation : A full understanding of brain functioning remains an unsolved challenge for science. In the last decade, neuroscientists conceived a revolutionary approach to reach this goal by proposing optogenetics (1), a genetic strategy to make neurons sensitive to light, such that the neuronal activity can be all-optically recorded and triggered by detecting and delivering light into the brain. This new research framework dramatically called into question physics as, once established that light can control neurons, new methodologies must be put in place to control the light across millions of neurons entwined in a scattering medium like the brain.
Two-photon excitation (2PE) (2) is at the moment the gold standard for in vivo functional imaging (3) and light-targeting photostimulation (4). Recently, novel strategies for functional volume imaging and holographic-based light shaping (5) enabled the extension of neuronal 2PE optical investigation to large population of neurons across a 3D volume (6–10). Nevertheless, light scattering limits 2PE investigations to superficial cortical areas extending only few hundred microns in the brain.

Aim : Aim of this PhD will be to study and implement strategies for in-depth all-optical circuits optogenetics able to overcome these limitations by integrating current approaches with three-photon excitation (3PE) (11, 12). The candidate will work on the design, the realization and the validation of 3PE light delivery systems based on ad hoc laser sources for 3P excitation featuring low-duty-cycle and high-energy pulses. Not only limited to neurobiology, the research outcomes are expected to step beyond giving more general physical insights to light-matter interaction and control of light in turbid media.

Funding : ERC Advanced Grant

References 1. O. Yizhar et al., Nature. 477, 171–8 (2011). 2. K. Svoboda, R. Yasuda, Neuron. 50, 823–39 (2006). 3. C. Grienberger, A. Konnerth, Neuron. 73, 862–85 (2012). 4. E. Ronzitti et al., Recent advances in patterned photostimulation for optogenetics. J. Opt. (2017). 5. E. Ronzitti, V. Emiliani, E. Papagiakoumou, Front. Cell. Neurosci. 12, 469 (2018). 6. A. M. Packer, L. E. Russell, H. W. P. Dalgleish, M. Häusser, Nat. Methods. 12, 140–6 (2015). 7. J. P. Rickgauer, K. Deisseroth, D. W. Tank, Simultaneous cellular-resolution optical perturbation and imaging of place cell firing fields. Nat. Neurosci. 17 (2014), pp. 1816–24. 8. A. R. Mardinly et al., Nat. Neurosci. 21, 881–893 (2018). 9. L. Carrillo-reid, W. Yang, Y. Bando, D. S. Peterka, R. Yuste, Science (80-. ). 353, 691–694 (2016). 10. I.-W. Chen et al., J. Neurosci., 1785–18 (2019). 11. N. G. Horton et al., Nat. Photonics. 7, 205–209 (2013). 12. C. Xu, W. W. Webb, J. Opt. Soc. Am. B. 13, 481 (1996).