Manipulation optique ciblée du comportement et des circuits neuronaux/ Using light for targeted interrogation of neural circuits and behaviour

Seminar organized by Valentina Emiliani & Michael Häusser from 13 – 18 September 2021.



Hillel Adesnik (Berkeley University, USA), Herwig Baier (Max Planck Institute of Neurobiology, Germany), Anne Beyeler (Université de Bordeaux, France), Karl Deisseroth (California Institute, USA), Stephane Dieudonne (INSERM, Lyon, France), Valentina Emiliani, (CNRS, INSERM, UPMC, Paris, France), Tommaso Fellin (Instituto Italiano de Tecnologia, Italy), Chris Harvey (Harvard University, USA), Michael Hausser (University College, London, UK), Peter Hegemann (Berlin University, Germany), Dustin Herrmann (University College, London, UK), Benjamin Judkewitz (Einstein Centre for neurociences, Berlin, Germany), Michael Lin (Stanford University, USA), Karim Oweiss (University of Florida, Miami, USA), Adam Packer (Oxford University, UK),  Darcy Peterka (Columbia University, USA), Botond Roska (Institute of Molecular and Clinical Ophtalmology, Basel, Switzerland), José Sahel (Institut de la vision, Paris), Johannes Vierock (Humbolt University of Berlin, Germany), Claire Wyart (Institut du Cerveau et de la Moëlle épinière, Paris, France), Ofer Yhizar (Weizmann Institute of Science), Zoe Zhang (UCL, London).



All-optical circuits manipulation: Holographic illumination combined with optogenetics enables to precisely activate single or multiple cells while recording the photo evoked response using Ca2+ or voltage imaging. Credit: François Blot

Les récents développements des sondes optogénétiques et des indicateurs d’activité neuronale génétiquement codés avec des nouveaux approaches de microscopie permettent désormais d’enregistrer et de manipuler l’activité des circuits neuronaux à l’aide de la lumière. Cette approche révolutionnaire “tout optique” est désormais suffisamment avancée pour permettre la lecture et la manipulation simultanées des neurones fonctionnellement définis dans le cerveau intact, avec une précision de la cellule unique. Ces progrès promettent d’éclairer de nombreux défis fondamentaux des neurosciences, notamment en permettent la recherche du code neuronal et des liens entre l’activité des circuits neuronaux et le comportement.

Cette réunion a été organisée pour rassembler les principaux développeurs d’outils et biologistes du monde entier travaillant dans une série de systèmes modèles afin d’évaluer l’état de l’art et de partager leurs derniers résultats, ainsi que d’identifier les limites techniques et les domaines de développement clés dans ce domaine en plein essor.






Dramatic recent developments in optogenetic probes, genetically encoded activity sensors, and novel microscopies now allow the activity of neural circuits to be both recorded and manipulated entirely using light. This revolutionary “all-optical” approach is now sufficiently advanced to enable simultaneous readout and manipulation of the same functionally defined neurons in the intact brain with single-neuron and single action potential precision. These advances promise to illuminate many fundamental challenges in neuroscience, including transforming our search for the neural code and the links between neural circuit activity and behaviour. This meeting has been organised to bring together the world’s leading tool developers and biologists working in a range of model systems to assess the state of the art and share their latest results, as well as to identify technical limitations and areas of key development in this rapidly developing field.



The meeting was organized in three sessions, grouping molecular probe developers, microscope developers, and neuroscientists using these advanced tools to answer key neurobiological questions. Each session was followed by a general discussion to summarize on the new approaches for all-optical interrogation, establish common standards, identify new opportunities and chart the future direction of this field.

Session 1  

The section was opened by the talk of Peter Hegemann who started with Georg Nagel the field of optogenetic with the discovery of channel-rhodopsins. His talk was followed by the talks of Ofer Yizhar, Adesnik Hillel, Johannes Vierock and Michael Lin presenting the most recent advances in the engineering of new genetic actuators and reporter. The session ended with a joint exposition from Botond Roska and José Sahel, presenting the most recent strategies to engineer optogenetic tools for human vison restoration and the first case of vision restoration in human.

Session 2

Opened by the talk of Valentina Emiliani, was grouping experts (Tomaso Fellin, Benjami Judkewitz, Darcy Peterka and Stephane Dieudonne) in the development of advanced illumination approach for all-optical brain interrogation, including holographic light patterning, temporal focussing, adaptive optics and fast laser scanning. The session enabled to review the last innovations made in the field to advance the scale, speed and fidelity of all-optical circuit interrogation.

The two sessions concluded with a general discussion to find a consensus on the best combination of currently available opsins and sensors and to express a wish list for opsin and sensor developers for minimizing crosstalk and maximizing photostimulation efficacy. The discussion also focused on identifying the fundamental limits to the achievable cellular resolution and numbers of cells and volumes that can be addressed using all-optical technology. Finally, the discussion focused on establishing protocols for assessing heating in brain tissue during all-optical experiments and strategies for minimizing heating effects and on finding agreed standards for calibration and validation of all-optical experiments across different model systems, and development of ‘ground truth’ datasets

Session 3

Opened by Adam Packer was grouping leading neurophysiologists (Claire Wyart, Herwig Baier, Anna Beyler, Michael Heusser, Karim Oweiss and Chriss Harvey) using advanced approaches for all-optical brain interrogation in different experimental paradigms, including zebra fish larvae, mice cortex and humans, on different spatial scales. The session has been closed by the talk of Karl Deisseroth who has pioneered the use of optogenetics for neuronal activity manipulation.

The session concluded with a general discussion on the key questions that could be solved given the available technology for brain interrogation. It emerged that the most promising fields of applications include hight throughput connectivity mapping, probe of the threshold for perception, investigation of memory dynamic. An interesting suggestion has also been to simplify the complexity of the circuits, in order to understand the basic mechanisms, by returning to simpler organisms (c-elegant, drosophila). In humans, the field that will likely o deliver results most rapidly seems to be vision restoration.

The most general conclusion of the meeting, was the awareness of the importance of the confluence of several complementary disciplines in modern neuroscience, including photonics, molecular biology, genetics, laser source development, neuroscience and medicine. This requires more than ever the ability to bring together actors from different disciplines around common discussions. In this respect this meeting at Les Treilles was a unique event. 



Peter Hegemann – Perspectives for photoreceptor developments

Ofer Yhizar – Optogenetic adventures at the Presynaptic Terminal

Hillel Adesnik – New tools for advancing the scale, speed and fidelity of all-optical circuit interrogation

Michael Lin – Optical recording of electrical activity in the nervous system: Sometimes you can get what you want

Johannes Vierock – Molecular tools for multicolor optogenetics

Botond Roska – Optogenetic therapy for Blindness

José Sahel – Translating Optogenics Into Clinical Trials

Valentina Emiliani – Holographic control of neuronal circuits

Tommaso Fellin – Optogenetic approaches for high-efficiency all-optical interrogation of neural circuits using blue-light-sensitive opsins

Darcy Peterka – Toward dynamics and control with 2P stimulation

Benjamin Judkewitz – Brain-wide microscopy

Stephane Dieudonne – Optical electrophysiology: how fast can it be?

Adam Packer – All-optical interrogation of neural circuits in vivo

Claire Wyart – Optogenetic’s double-edged sword: In Vivo efficacy, reliability and … calibration?

Herwig Baier – A changing view of the visual system — the zebrafish perspective

Anne Beyeler- Ally fiber photometry and optogenetics to dissect circuits: case study of the insular cortex

Michael Hausser / Zoe Zhang /Dustin Herrmann – Using all-optical interrogation to probe circuits and dendrites during behaviour

Karim Oweiss – All-optical interrogation of population dynamics: implication for neuronal circuit function and disfunction

Chris Harvey – Cortical networks for flexible decisions during spatial navigation

Karl Deisseroth – Inner Workings And Applications Of Pump-Like Channelrhodopsins





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