An optogenetic method for investigating presynaptic molecular regulation

Abstract While efficient methods are well established for studying postsynaptic protein regulation of glutamatergic synapses in the mammalian central nervous system, similarly efficient methods are lacking for studying proteins regulating presynaptic function. In the present study, we introduce an o...

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Autores principales:	Yuni Kay, Bruce E. Herring
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a73efe5c276c44279785013b07fd3665
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spelling	oai:doaj.org-article:a73efe5c276c44279785013b07fd36652021-12-02T15:56:49ZAn optogenetic method for investigating presynaptic molecular regulation10.1038/s41598-021-90244-02045-2322https://doaj.org/article/a73efe5c276c44279785013b07fd36652021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90244-0https://doaj.org/toc/2045-2322Abstract While efficient methods are well established for studying postsynaptic protein regulation of glutamatergic synapses in the mammalian central nervous system, similarly efficient methods are lacking for studying proteins regulating presynaptic function. In the present study, we introduce an optical/electrophysiological method for investigating presynaptic molecular regulation. Here, using an optogenetic approach, we selectively stimulate genetically modified presynaptic CA3 pyramidal neurons in the hippocampus and measure optically-induced excitatory postsynaptic currents produced in unmodified postsynaptic CA1 pyramidal neurons. While such use of optogenetics is not novel, previous implementation methods do not allow basic quantification of the changes in synaptic strength produced by genetic manipulations. We find that incorporating simultaneous recordings of fiber volley amplitude provides a control for optical stimulation intensity and, as a result, creates a metric of synaptic efficacy that can be compared across experimental conditions. In the present study, we utilize our new method to demonstrate that inhibition of synaptotagmin 1 expression in CA3 pyramidal neurons leads to a significant reduction in Schaffer collateral synapse function, an effect that is masked with conventional electrical stimulation. Our hope is that this method will expedite our understanding of molecular regulatory pathways that govern presynaptic function.Yuni KayBruce E. HerringNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yuni Kay Bruce E. Herring An optogenetic method for investigating presynaptic molecular regulation
description	Abstract While efficient methods are well established for studying postsynaptic protein regulation of glutamatergic synapses in the mammalian central nervous system, similarly efficient methods are lacking for studying proteins regulating presynaptic function. In the present study, we introduce an optical/electrophysiological method for investigating presynaptic molecular regulation. Here, using an optogenetic approach, we selectively stimulate genetically modified presynaptic CA3 pyramidal neurons in the hippocampus and measure optically-induced excitatory postsynaptic currents produced in unmodified postsynaptic CA1 pyramidal neurons. While such use of optogenetics is not novel, previous implementation methods do not allow basic quantification of the changes in synaptic strength produced by genetic manipulations. We find that incorporating simultaneous recordings of fiber volley amplitude provides a control for optical stimulation intensity and, as a result, creates a metric of synaptic efficacy that can be compared across experimental conditions. In the present study, we utilize our new method to demonstrate that inhibition of synaptotagmin 1 expression in CA3 pyramidal neurons leads to a significant reduction in Schaffer collateral synapse function, an effect that is masked with conventional electrical stimulation. Our hope is that this method will expedite our understanding of molecular regulatory pathways that govern presynaptic function.
format	article
author	Yuni Kay Bruce E. Herring
author_facet	Yuni Kay Bruce E. Herring
author_sort	Yuni Kay
title	An optogenetic method for investigating presynaptic molecular regulation
title_short	An optogenetic method for investigating presynaptic molecular regulation
title_full	An optogenetic method for investigating presynaptic molecular regulation
title_fullStr	An optogenetic method for investigating presynaptic molecular regulation
title_full_unstemmed	An optogenetic method for investigating presynaptic molecular regulation
title_sort	optogenetic method for investigating presynaptic molecular regulation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a73efe5c276c44279785013b07fd3665
work_keys_str_mv	AT yunikay anoptogeneticmethodforinvestigatingpresynapticmolecularregulation AT bruceeherring anoptogeneticmethodforinvestigatingpresynapticmolecularregulation AT yunikay optogeneticmethodforinvestigatingpresynapticmolecularregulation AT bruceeherring optogeneticmethodforinvestigatingpresynapticmolecularregulation
_version_	1718385410834432000

An optogenetic method for investigating presynaptic molecular regulation

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