Development of an optogenetic toolkit for neural circuit dissection in squirrel monkeys

Abstract Optogenetic tools have opened a rich experimental landscape for understanding neural function and disease. Here, we present the first validation of eight optogenetic constructs driven by recombinant adeno-associated virus (AAV) vectors and a WGA-Cre based dual injection strategy for project...

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Autores principales:	Daniel J. O’Shea, Paul Kalanithi, Emily A. Ferenczi, Brian Hsueh, Chandramouli Chandrasekaran, Werapong Goo, Ilka Diester, Charu Ramakrishnan, Matthew T. Kaufman, Stephen I. Ryu, Kristen W. Yeom, Karl Deisseroth, Krishna V. Shenoy
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/06230dc486274d2584a529f403050899
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spelling	oai:doaj.org-article:06230dc486274d2584a529f4030508992021-12-02T11:40:54ZDevelopment of an optogenetic toolkit for neural circuit dissection in squirrel monkeys10.1038/s41598-018-24362-72045-2322https://doaj.org/article/06230dc486274d2584a529f4030508992018-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-24362-7https://doaj.org/toc/2045-2322Abstract Optogenetic tools have opened a rich experimental landscape for understanding neural function and disease. Here, we present the first validation of eight optogenetic constructs driven by recombinant adeno-associated virus (AAV) vectors and a WGA-Cre based dual injection strategy for projection targeting in a widely-used New World primate model, the common squirrel monkey Saimiri sciureus. We observed opsin expression around the local injection site and in axonal projections to downstream regions, as well as transduction to thalamic neurons, resembling expression patterns observed in macaques. Optical stimulation drove strong, reliable excitatory responses in local neural populations for two depolarizing opsins in anesthetized monkeys. Finally, we observed continued, healthy opsin expression for at least one year. These data suggest that optogenetic tools can be readily applied in squirrel monkeys, an important first step in enabling precise, targeted manipulation of neural circuits in these highly trainable, cognitively sophisticated animals. In conjunction with similar approaches in macaques and marmosets, optogenetic manipulation of neural circuits in squirrel monkeys will provide functional, comparative insights into neural circuits which subserve dextrous motor control as well as other adaptive behaviors across the primate lineage. Additionally, development of these tools in squirrel monkeys, a well-established model system for several human neurological diseases, can aid in identifying novel treatment strategies.Daniel J. O’SheaPaul KalanithiEmily A. FerencziBrian HsuehChandramouli ChandrasekaranWerapong GooIlka DiesterCharu RamakrishnanMatthew T. KaufmanStephen I. RyuKristen W. YeomKarl DeisserothKrishna V. ShenoyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-20 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daniel J. O’Shea Paul Kalanithi Emily A. Ferenczi Brian Hsueh Chandramouli Chandrasekaran Werapong Goo Ilka Diester Charu Ramakrishnan Matthew T. Kaufman Stephen I. Ryu Kristen W. Yeom Karl Deisseroth Krishna V. Shenoy Development of an optogenetic toolkit for neural circuit dissection in squirrel monkeys
description	Abstract Optogenetic tools have opened a rich experimental landscape for understanding neural function and disease. Here, we present the first validation of eight optogenetic constructs driven by recombinant adeno-associated virus (AAV) vectors and a WGA-Cre based dual injection strategy for projection targeting in a widely-used New World primate model, the common squirrel monkey Saimiri sciureus. We observed opsin expression around the local injection site and in axonal projections to downstream regions, as well as transduction to thalamic neurons, resembling expression patterns observed in macaques. Optical stimulation drove strong, reliable excitatory responses in local neural populations for two depolarizing opsins in anesthetized monkeys. Finally, we observed continued, healthy opsin expression for at least one year. These data suggest that optogenetic tools can be readily applied in squirrel monkeys, an important first step in enabling precise, targeted manipulation of neural circuits in these highly trainable, cognitively sophisticated animals. In conjunction with similar approaches in macaques and marmosets, optogenetic manipulation of neural circuits in squirrel monkeys will provide functional, comparative insights into neural circuits which subserve dextrous motor control as well as other adaptive behaviors across the primate lineage. Additionally, development of these tools in squirrel monkeys, a well-established model system for several human neurological diseases, can aid in identifying novel treatment strategies.
format	article
author	Daniel J. O’Shea Paul Kalanithi Emily A. Ferenczi Brian Hsueh Chandramouli Chandrasekaran Werapong Goo Ilka Diester Charu Ramakrishnan Matthew T. Kaufman Stephen I. Ryu Kristen W. Yeom Karl Deisseroth Krishna V. Shenoy
author_facet	Daniel J. O’Shea Paul Kalanithi Emily A. Ferenczi Brian Hsueh Chandramouli Chandrasekaran Werapong Goo Ilka Diester Charu Ramakrishnan Matthew T. Kaufman Stephen I. Ryu Kristen W. Yeom Karl Deisseroth Krishna V. Shenoy
author_sort	Daniel J. O’Shea
title	Development of an optogenetic toolkit for neural circuit dissection in squirrel monkeys
title_short	Development of an optogenetic toolkit for neural circuit dissection in squirrel monkeys
title_full	Development of an optogenetic toolkit for neural circuit dissection in squirrel monkeys
title_fullStr	Development of an optogenetic toolkit for neural circuit dissection in squirrel monkeys
title_full_unstemmed	Development of an optogenetic toolkit for neural circuit dissection in squirrel monkeys
title_sort	development of an optogenetic toolkit for neural circuit dissection in squirrel monkeys
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/06230dc486274d2584a529f403050899
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Development of an optogenetic toolkit for neural circuit dissection in squirrel monkeys

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