Flexible and stretchable polymer optical fibers for chronic brain and vagus nerve optogenetic stimulations in free-behaving animals

Abstract Background Although electrical stimulation of the peripheral and central nervous systems has attracted much attention owing to its potential therapeutic effects on neuropsychiatric diseases, its non-cell-type-specific activation characteristics may hinder its wide clinical application. Unli...

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Autores principales:	Yi Cao, Suwan Pan, Mengying Yan, Chongyang Sun, Jianyu Huang, Cheng Zhong, Liping Wang, Lu Yi
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Optogenetics Flexible optical fibers Brain stimulation Vagus nerve stimulation Anxiety-like behavior Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/b532bcd7b6d8486e8744b326635e07e1
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spelling	oai:doaj.org-article:b532bcd7b6d8486e8744b326635e07e12021-11-28T12:41:16ZFlexible and stretchable polymer optical fibers for chronic brain and vagus nerve optogenetic stimulations in free-behaving animals10.1186/s12915-021-01187-x1741-7007https://doaj.org/article/b532bcd7b6d8486e8744b326635e07e12021-11-01T00:00:00Zhttps://doi.org/10.1186/s12915-021-01187-xhttps://doaj.org/toc/1741-7007Abstract Background Although electrical stimulation of the peripheral and central nervous systems has attracted much attention owing to its potential therapeutic effects on neuropsychiatric diseases, its non-cell-type-specific activation characteristics may hinder its wide clinical application. Unlike electrical methodologies, optogenetics has more recently been applied as a cell-specific approach for precise modulation of neural functions in vivo, for instance on the vagus nerve. The commonly used implantable optical waveguides are silica optical fibers, which for brain optogenetic stimulation (BOS) are usually fixed on the skull bone. However, due to the huge mismatch of mechanical properties between the stiff optical implants and deformable vagal tissues, vagus nerve optogenetic stimulation (VNOS) in free-behaving animals continues to be a great challenge. Results To resolve this issue, we developed a simplified method for the fabrication of flexible and stretchable polymer optical fibers (POFs), which show significantly improved characteristics for in vivo optogenetic applications, specifically a low Young’s modulus, high stretchability, improved biocompatibility, and long-term stability. We implanted the POFs into the primary motor cortex of C57 mice after the expression of CaMKIIα-ChR2-mCherry detected frequency-dependent neuronal activity and the behavioral changes during light delivery. The viability of POFs as implantable waveguides for VNOS was verified by the increased firing rate of the fast-spiking GABAergic interneurons recorded in the left vagus nerve of VGAT-ChR2 transgenic mice. Furthermore, VNOS was carried out in free-moving rodents via chronically implanted POFs, and an inhibitory influence on the cardiac system and an anxiolytic effect on behaviors was shown. Conclusion Our results demonstrate the feasibility and advantages of the use of POFs in chronic optogenetic modulations in both of the central and peripheral nervous systems, providing new information for the development of novel therapeutic strategies for the treatment of neuropsychiatric disorders.Yi CaoSuwan PanMengying YanChongyang SunJianyu HuangCheng ZhongLiping WangLu YiBMCarticleOptogeneticsFlexible optical fibersBrain stimulationVagus nerve stimulationAnxiety-like behaviorBiology (General)QH301-705.5ENBMC Biology, Vol 19, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Optogenetics Flexible optical fibers Brain stimulation Vagus nerve stimulation Anxiety-like behavior Biology (General) QH301-705.5
spellingShingle	Optogenetics Flexible optical fibers Brain stimulation Vagus nerve stimulation Anxiety-like behavior Biology (General) QH301-705.5 Yi Cao Suwan Pan Mengying Yan Chongyang Sun Jianyu Huang Cheng Zhong Liping Wang Lu Yi Flexible and stretchable polymer optical fibers for chronic brain and vagus nerve optogenetic stimulations in free-behaving animals
description	Abstract Background Although electrical stimulation of the peripheral and central nervous systems has attracted much attention owing to its potential therapeutic effects on neuropsychiatric diseases, its non-cell-type-specific activation characteristics may hinder its wide clinical application. Unlike electrical methodologies, optogenetics has more recently been applied as a cell-specific approach for precise modulation of neural functions in vivo, for instance on the vagus nerve. The commonly used implantable optical waveguides are silica optical fibers, which for brain optogenetic stimulation (BOS) are usually fixed on the skull bone. However, due to the huge mismatch of mechanical properties between the stiff optical implants and deformable vagal tissues, vagus nerve optogenetic stimulation (VNOS) in free-behaving animals continues to be a great challenge. Results To resolve this issue, we developed a simplified method for the fabrication of flexible and stretchable polymer optical fibers (POFs), which show significantly improved characteristics for in vivo optogenetic applications, specifically a low Young’s modulus, high stretchability, improved biocompatibility, and long-term stability. We implanted the POFs into the primary motor cortex of C57 mice after the expression of CaMKIIα-ChR2-mCherry detected frequency-dependent neuronal activity and the behavioral changes during light delivery. The viability of POFs as implantable waveguides for VNOS was verified by the increased firing rate of the fast-spiking GABAergic interneurons recorded in the left vagus nerve of VGAT-ChR2 transgenic mice. Furthermore, VNOS was carried out in free-moving rodents via chronically implanted POFs, and an inhibitory influence on the cardiac system and an anxiolytic effect on behaviors was shown. Conclusion Our results demonstrate the feasibility and advantages of the use of POFs in chronic optogenetic modulations in both of the central and peripheral nervous systems, providing new information for the development of novel therapeutic strategies for the treatment of neuropsychiatric disorders.
format	article
author	Yi Cao Suwan Pan Mengying Yan Chongyang Sun Jianyu Huang Cheng Zhong Liping Wang Lu Yi
author_facet	Yi Cao Suwan Pan Mengying Yan Chongyang Sun Jianyu Huang Cheng Zhong Liping Wang Lu Yi
author_sort	Yi Cao
title	Flexible and stretchable polymer optical fibers for chronic brain and vagus nerve optogenetic stimulations in free-behaving animals
title_short	Flexible and stretchable polymer optical fibers for chronic brain and vagus nerve optogenetic stimulations in free-behaving animals
title_full	Flexible and stretchable polymer optical fibers for chronic brain and vagus nerve optogenetic stimulations in free-behaving animals
title_fullStr	Flexible and stretchable polymer optical fibers for chronic brain and vagus nerve optogenetic stimulations in free-behaving animals
title_full_unstemmed	Flexible and stretchable polymer optical fibers for chronic brain and vagus nerve optogenetic stimulations in free-behaving animals
title_sort	flexible and stretchable polymer optical fibers for chronic brain and vagus nerve optogenetic stimulations in free-behaving animals
publisher	BMC
publishDate	2021
url	https://doaj.org/article/b532bcd7b6d8486e8744b326635e07e1
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Flexible and stretchable polymer optical fibers for chronic brain and vagus nerve optogenetic stimulations in free-behaving animals

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