The spatial pattern of light determines the kinetics and modulates backpropagation of optogenetic action potentials

Optogenetics offers an unprecedented ability to spatially target neuronal stimulations. This study investigated via simulation, for the first time, how the spatial pattern of excitation affects the response of channelrhodopsin-2 (ChR2) expressing neurons. First we described a methodology for modelin...

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Main Authors:	Grossman, Nir, Simiaki, Vasiliki, Martinet, Claire, Toumazou, Christofer, Schultz, Simon R., Nikolic, Konstantin
Format:	Online
Language:	English
Published:	Springer US 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3650242/

id	pubmed-3650242
recordtype	oai_dc
spelling	pubmed-36502422013-05-10 The spatial pattern of light determines the kinetics and modulates backpropagation of optogenetic action potentials Grossman, Nir Simiaki, Vasiliki Martinet, Claire Toumazou, Christofer Schultz, Simon R. Nikolic, Konstantin Article Optogenetics offers an unprecedented ability to spatially target neuronal stimulations. This study investigated via simulation, for the first time, how the spatial pattern of excitation affects the response of channelrhodopsin-2 (ChR2) expressing neurons. First we described a methodology for modeling ChR2 in the NEURON simulation platform. Then, we compared four most commonly considered illumination strategies (somatic, dendritic, axonal and whole cell) in a paradigmatic model of a cortical layer V pyramidal cell. We show that the spatial pattern of illumination has an important impact on the efficiency of stimulation and the kinetics of the spiking output. Whole cell illumination synchronizes the depolarization of the dendritic tree and the soma and evokes spiking characteristics with a distinct pattern including an increased bursting rate and enhanced back propagation of action potentials (bAPs). This type of illumination is the most efficient as a given irradiance threshold was achievable with only 6 % of ChR2 density needed in the case of somatic illumination. Targeting only the axon initial segment requires a high ChR2 density to achieve a given threshold irradiance and a prolonged illumination does not yield sustained spiking. We also show that patterned illumination can be used to modulate the bAPs and hence spatially modulate the direction and amplitude of spike time dependent plasticity protocols. We further found the irradiance threshold to increase in proportion to the demyelination level of an axon, suggesting that measurements of the irradiance threshold (for example relative to the soma) could be used to remotely probe a loss of neural myelin sheath, which is a hallmark of several neurodegenerative diseases. Springer US 2012-11-22 2013-06 /pmc/articles/PMC3650242/ /pubmed/23179855 http://dx.doi.org/10.1007/s10827-012-0431-7 Text en © Springer Science+Business Media New York 2012
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Grossman, Nir Simiaki, Vasiliki Martinet, Claire Toumazou, Christofer Schultz, Simon R. Nikolic, Konstantin
spellingShingle	Grossman, Nir Simiaki, Vasiliki Martinet, Claire Toumazou, Christofer Schultz, Simon R. Nikolic, Konstantin The spatial pattern of light determines the kinetics and modulates backpropagation of optogenetic action potentials
author_facet	Grossman, Nir Simiaki, Vasiliki Martinet, Claire Toumazou, Christofer Schultz, Simon R. Nikolic, Konstantin
author_sort	Grossman, Nir
title	The spatial pattern of light determines the kinetics and modulates backpropagation of optogenetic action potentials
title_short	The spatial pattern of light determines the kinetics and modulates backpropagation of optogenetic action potentials
title_full	The spatial pattern of light determines the kinetics and modulates backpropagation of optogenetic action potentials
title_fullStr	The spatial pattern of light determines the kinetics and modulates backpropagation of optogenetic action potentials
title_full_unstemmed	The spatial pattern of light determines the kinetics and modulates backpropagation of optogenetic action potentials
title_sort	spatial pattern of light determines the kinetics and modulates backpropagation of optogenetic action potentials
description	Optogenetics offers an unprecedented ability to spatially target neuronal stimulations. This study investigated via simulation, for the first time, how the spatial pattern of excitation affects the response of channelrhodopsin-2 (ChR2) expressing neurons. First we described a methodology for modeling ChR2 in the NEURON simulation platform. Then, we compared four most commonly considered illumination strategies (somatic, dendritic, axonal and whole cell) in a paradigmatic model of a cortical layer V pyramidal cell. We show that the spatial pattern of illumination has an important impact on the efficiency of stimulation and the kinetics of the spiking output. Whole cell illumination synchronizes the depolarization of the dendritic tree and the soma and evokes spiking characteristics with a distinct pattern including an increased bursting rate and enhanced back propagation of action potentials (bAPs). This type of illumination is the most efficient as a given irradiance threshold was achievable with only 6 % of ChR2 density needed in the case of somatic illumination. Targeting only the axon initial segment requires a high ChR2 density to achieve a given threshold irradiance and a prolonged illumination does not yield sustained spiking. We also show that patterned illumination can be used to modulate the bAPs and hence spatially modulate the direction and amplitude of spike time dependent plasticity protocols. We further found the irradiance threshold to increase in proportion to the demyelination level of an axon, suggesting that measurements of the irradiance threshold (for example relative to the soma) could be used to remotely probe a loss of neural myelin sheath, which is a hallmark of several neurodegenerative diseases.
publisher	Springer US
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3650242/
_version_	1611976772339892224

The spatial pattern of light determines the kinetics and modulates backpropagation of optogenetic action potentials

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