Advantages, Pitfalls, and Developments of All Optical Interrogation Strategies of Microcircuits in vivo

The holy grail for every neurophysiologist is to conclude a causal relationship between an elementary behaviour and the function of a specific brain area or circuit. Our effort to map elementary behaviours to specific brain loci and to further manipulate neural activity while observing the alteratio...

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Main Authors: Stylianos Papaioannou, Paolo Medini
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-06-01
Series:Frontiers in Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnins.2022.859803/full
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author Stylianos Papaioannou
Paolo Medini
author_facet Stylianos Papaioannou
Paolo Medini
author_sort Stylianos Papaioannou
collection DOAJ
description The holy grail for every neurophysiologist is to conclude a causal relationship between an elementary behaviour and the function of a specific brain area or circuit. Our effort to map elementary behaviours to specific brain loci and to further manipulate neural activity while observing the alterations in behaviour is in essence the goal for neuroscientists. Recent advancements in the area of experimental brain imaging in the form of longer wavelength near infrared (NIR) pulsed lasers with the development of highly efficient optogenetic actuators and reporters of neural activity, has endowed us with unprecedented resolution in spatiotemporal precision both in imaging neural activity as well as manipulating it with multiphoton microscopy. This readily available toolbox has introduced a so called all-optical physiology and interrogation of circuits and has opened new horizons when it comes to precisely, fast and non-invasively map and manipulate anatomically, molecularly or functionally identified mesoscopic brain circuits. The purpose of this review is to describe the advantages and possible pitfalls of all-optical approaches in system neuroscience, where by all-optical we mean use of multiphoton microscopy to image the functional response of neuron(s) in the network so to attain flexible choice of the cells to be also optogenetically photostimulated by holography, in absence of electrophysiology. Spatio-temporal constraints will be compared toward the classical reference of electrophysiology methods. When appropriate, in relation to current limitations of current optical approaches, we will make reference to latest works aimed to overcome these limitations, in order to highlight the most recent developments. We will also provide examples of types of experiments uniquely approachable all-optically. Finally, although mechanically non-invasive, all-optical electrophysiology exhibits potential off-target effects which can ambiguate and complicate the interpretation of the results. In summary, this review is an effort to exemplify how an all-optical experiment can be designed, conducted and interpreted from the point of view of the integrative neurophysiologist.
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spelling doaj.art-1e28930bea294cc59e6ffcfeb8055e732022-12-22T02:33:43ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2022-06-011610.3389/fnins.2022.859803859803Advantages, Pitfalls, and Developments of All Optical Interrogation Strategies of Microcircuits in vivoStylianos PapaioannouPaolo MediniThe holy grail for every neurophysiologist is to conclude a causal relationship between an elementary behaviour and the function of a specific brain area or circuit. Our effort to map elementary behaviours to specific brain loci and to further manipulate neural activity while observing the alterations in behaviour is in essence the goal for neuroscientists. Recent advancements in the area of experimental brain imaging in the form of longer wavelength near infrared (NIR) pulsed lasers with the development of highly efficient optogenetic actuators and reporters of neural activity, has endowed us with unprecedented resolution in spatiotemporal precision both in imaging neural activity as well as manipulating it with multiphoton microscopy. This readily available toolbox has introduced a so called all-optical physiology and interrogation of circuits and has opened new horizons when it comes to precisely, fast and non-invasively map and manipulate anatomically, molecularly or functionally identified mesoscopic brain circuits. The purpose of this review is to describe the advantages and possible pitfalls of all-optical approaches in system neuroscience, where by all-optical we mean use of multiphoton microscopy to image the functional response of neuron(s) in the network so to attain flexible choice of the cells to be also optogenetically photostimulated by holography, in absence of electrophysiology. Spatio-temporal constraints will be compared toward the classical reference of electrophysiology methods. When appropriate, in relation to current limitations of current optical approaches, we will make reference to latest works aimed to overcome these limitations, in order to highlight the most recent developments. We will also provide examples of types of experiments uniquely approachable all-optically. Finally, although mechanically non-invasive, all-optical electrophysiology exhibits potential off-target effects which can ambiguate and complicate the interpretation of the results. In summary, this review is an effort to exemplify how an all-optical experiment can be designed, conducted and interpreted from the point of view of the integrative neurophysiologist.https://www.frontiersin.org/articles/10.3389/fnins.2022.859803/fullnetwork functional imagingholographic optogeneticsall-optical circuit interrogationmultiphoton microscopyin vivo electrophysiology
spellingShingle Stylianos Papaioannou
Paolo Medini
Advantages, Pitfalls, and Developments of All Optical Interrogation Strategies of Microcircuits in vivo
Frontiers in Neuroscience
network functional imaging
holographic optogenetics
all-optical circuit interrogation
multiphoton microscopy
in vivo electrophysiology
title Advantages, Pitfalls, and Developments of All Optical Interrogation Strategies of Microcircuits in vivo
title_full Advantages, Pitfalls, and Developments of All Optical Interrogation Strategies of Microcircuits in vivo
title_fullStr Advantages, Pitfalls, and Developments of All Optical Interrogation Strategies of Microcircuits in vivo
title_full_unstemmed Advantages, Pitfalls, and Developments of All Optical Interrogation Strategies of Microcircuits in vivo
title_short Advantages, Pitfalls, and Developments of All Optical Interrogation Strategies of Microcircuits in vivo
title_sort advantages pitfalls and developments of all optical interrogation strategies of microcircuits in vivo
topic network functional imaging
holographic optogenetics
all-optical circuit interrogation
multiphoton microscopy
in vivo electrophysiology
url https://www.frontiersin.org/articles/10.3389/fnins.2022.859803/full
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