Understanding communication between neurons, who is talking to whom, and what language they are speaking, is essential for discovering how brain circuits underlie brain function and dysfunction. Over the past decades, Neuroscience has made exponential progress toward recording and imaging communication between neurons. In addition, geneticists have recently developed the capability to manipulate neurons with light through the expression of light-activated microbial proteins called """"""""opsins."""""""" Now, neuroscientists can drive neural circuits in order to determine how they give rise to sensation, perception, and cognitive function. In order to take full advantage of """"""""optogenetic"""""""" tools, we are developing holographic methods to deliver patterned light into brain tissue, to enable simultaneous activation of multiple neurons, independently controlling the strength and timing of light targeted to each cell. Here, we propose to: (1) characterize newly developed opsins to determine which are best suited for holographic activation techniques;(2) implement holographic light patterns in three-dimensions;and, (3) distribute and iteratively optimize the 3D holography system in collaboration with Neuroscientists studying circuits in optically and physiologically diverse neura systems. The end goal is to develop a robust system, capable of manipulating neurons in patterns that mimic naturally occurring activity. Insights gained through this collaborative optimization will be used to inform the design of the commercial prototype developed by our industry collaborator Intelligent Imaging Innovations, Inc. (Denver, CO). The system can thus be widely distributed for neural circuit investigation, both in-vitro and in-vivo, to discover how neual communication gives rise to sensation, perception, cognition, and behavior. Such insights will improve our ability to identify effective targets and methods for treating neurological diseases and disorders.

Public Health Relevance

The goal of three-dimensional holography is to enable Neuroscientists to manipulate neural circuits in order to discover how patterns of activity relate to sensation, perception and cognition. This capability is essential for discovering how communication between neurons gives rise to healthy brain function. These insights will improve our ability to identify effective targets and methods for treating neurological diseases and disorders.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project--Cooperative Agreements (U01)
Project #
Application #
Study Section
Special Emphasis Panel (ZNS1-SRB-G (77))
Program Officer
Talley, Edmund M
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Pierre and Marie Curie University
Zip Code
Chaigneau, Emmanuelle; Ronzitti, Emiliano; Gajowa, Marta A et al. (2016) Two-Photon Holographic Stimulation of ReaChR. Front Cell Neurosci 10:234
Conti, Rossella; Assayag, Osnath; de Sars, Vincent et al. (2016) Computer Generated Holography with Intensity-Graded Patterns. Front Cell Neurosci 10:236
Hernandez, Oscar; Papagiakoumou, Eirini; Tanese, Dimitrii et al. (2016) Three-dimensional spatiotemporal focusing of holographic patterns. Nat Commun 7:11928
Gardella, Christophe; Marre, Olivier; Mora, Thierry (2016) A Tractable Method for Describing Complex Couplings between Neurons and Population Rate. eNeuro 3:
Emiliani, Valentina; Cohen, Adam E; Deisseroth, Karl et al. (2015) All-Optical Interrogation of Neural Circuits. J Neurosci 35:13917-26
Lauterbach, Marcel A; Ronzitti, Emiliano; Sternberg, Jenna R et al. (2015) Fast Calcium Imaging with Optical Sectioning via HiLo Microscopy. PLoS One 10:e0143681