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All-optical neurophysiology
ALL-OPTICAL NEUROPHYSIOLOGY WITH HOLOGRAPHIC LIGHT SHAPING
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Christiane GRIMM and Valentina EMILIANI * Institute de la Vision, Sorbonne Université, INSERM, CNRS, Paris, France * valentina. emiliani @ inserm. fr
https:// doi. org / 10.1051 / photon / 202513426
This is an Open Access article distributed under the terms of the Creative Commons Attribution License( https:// creativecommons. org / licenses / by / 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
To unravel how the mammalian brain computes in health and disease, neuroscientists need techniques that can non-invasively interrogate and manipulate neuronal activity with high spatiotemporal precision. In recent years, new approaches have emerged to achieve this goal by combining advanced light-shaping optical methods, two-photon excitation, and genetic tools for calcium, voltage imaging and optogenetics. Here, we provide a brief overview of these approaches, which lay the foundation for fully optical neurophysiology in both head-restrained and freely moving animals.
OPTICAL NEUROPHYSIOLOGY Understanding brain function requires the investigation of neuronal circuitry across multiple spatiotemporal scales with the goal to map circuit activity and identify the respective behavioral correlates. One fundamental question is how these circuits operate: How are neurons connected within the circuit and to other circuits? Are individual neurons equivalent or do they form hierarchically organized assemblies? Do certain cells act as hubs orchestrating circuit activity and to what extent is a given spatiotemporal firing pattern necessary and unique for a particular behavior?
Answering these questions requires the ability to observe and also manipulate circuit activity with single-cell and single spike precision. Electrophysiological approaches can provide single-cell resolution when using intracellular electrodes, or population-level information when employing multi-electrode arrays and have greatly advanced the understanding of circuit dynamics to date. However, recordings at cellular resolution are low in throughput while population recordings lack single-cell resolution. In general, electrical techniques offer no access to the genetic identity of the recorded cells and are inherently invasive. In the case of intracellular recordings, this contact is even more disruptive and not compatible with longitudinal studies that require stable recordings over extended periods.
To overcome the limitations of electrical recordings, a collaborative effort among molecular biologists, physicists, biophysicists, and chemists has aimed to replace electrodes with light, both to read and manipulate electrical activity non-invasively, holding high potential especially for neuroscience applications. This interdisciplinary effort has given rise to the field of all-optical neurophysiology [ 1 ], which combines the genetic specificity of molecular tools with the
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