Efficiency of cell-type specific and generic promoters in transducing oxytocin neurons and monitoring their neural activity during lactation

Abstract Hypothalamic oxytocin (OXT) and arginine-vasopressin (AVP) neurons have been at the center of several physiological and behavioral studies. Advances in viral vector biology and the development of transgenic rodent models have allowed for targeted gene expression to study the functions of sp...

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Main Authors: Keerthi Thirtamara Rajamani, Amanda B. Leithead, Michelle Kim, Marie Barbier, Michael Peruggia, Kristi Niblo, Lara Barteczko, Arthur Lefevre, Valery Grinevich, Hala Harony-Nicolas
Format: Article
Language:English
Published: Nature Portfolio 2021-11-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-01818-x
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author Keerthi Thirtamara Rajamani
Amanda B. Leithead
Michelle Kim
Marie Barbier
Michael Peruggia
Kristi Niblo
Lara Barteczko
Arthur Lefevre
Valery Grinevich
Hala Harony-Nicolas
author_facet Keerthi Thirtamara Rajamani
Amanda B. Leithead
Michelle Kim
Marie Barbier
Michael Peruggia
Kristi Niblo
Lara Barteczko
Arthur Lefevre
Valery Grinevich
Hala Harony-Nicolas
author_sort Keerthi Thirtamara Rajamani
collection DOAJ
description Abstract Hypothalamic oxytocin (OXT) and arginine-vasopressin (AVP) neurons have been at the center of several physiological and behavioral studies. Advances in viral vector biology and the development of transgenic rodent models have allowed for targeted gene expression to study the functions of specific cell populations and brain circuits. In this study, we compared the efficiency of various adeno-associated viral vectors in these cell populations and demonstrated that none of the widely used promoters were, on their own, effective at driving expression of a down-stream fluorescent protein in OXT or AVP neurons. As anticipated, the OXT promoter could efficiently drive gene expression in OXT neurons and this efficiency is solely attributed to the promoter and not the viral serotype. We also report that a dual virus approach using an OXT promoter driven Cre recombinase significantly improved the efficiency of viral transduction in OXT neurons. Finally, we demonstrate the utility of the OXT promoter for conducting functional studies on OXT neurons by using an OXT specific viral system to record neural activity of OXT neurons in lactating female rats across time. We conclude that extreme caution is needed when employing non-neuron-specific viral approaches/promoters to study neural populations within the paraventricular nucleus of the hypothalamus.
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spelling doaj.art-bdc99ed306914c47bc827e82cdc68a642022-12-21T23:38:36ZengNature PortfolioScientific Reports2045-23222021-11-0111111410.1038/s41598-021-01818-xEfficiency of cell-type specific and generic promoters in transducing oxytocin neurons and monitoring their neural activity during lactationKeerthi Thirtamara Rajamani0Amanda B. Leithead1Michelle Kim2Marie Barbier3Michael Peruggia4Kristi Niblo5Lara Barteczko6Arthur Lefevre7Valery Grinevich8Hala Harony-Nicolas9Department of Psychiatry, Icahn School of Medicine at Mount SinaiDepartment of Psychiatry, Icahn School of Medicine at Mount SinaiDepartment of Psychiatry, Icahn School of Medicine at Mount SinaiDepartment of Psychiatry, Icahn School of Medicine at Mount SinaiDepartment of Psychiatry, Icahn School of Medicine at Mount SinaiDepartment of Psychiatry, Icahn School of Medicine at Mount SinaiDepartment of Neuropeptide Research in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of HeidelbergDepartment of Neuropeptide Research in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of HeidelbergDepartment of Neuropeptide Research in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of HeidelbergDepartment of Psychiatry, Icahn School of Medicine at Mount SinaiAbstract Hypothalamic oxytocin (OXT) and arginine-vasopressin (AVP) neurons have been at the center of several physiological and behavioral studies. Advances in viral vector biology and the development of transgenic rodent models have allowed for targeted gene expression to study the functions of specific cell populations and brain circuits. In this study, we compared the efficiency of various adeno-associated viral vectors in these cell populations and demonstrated that none of the widely used promoters were, on their own, effective at driving expression of a down-stream fluorescent protein in OXT or AVP neurons. As anticipated, the OXT promoter could efficiently drive gene expression in OXT neurons and this efficiency is solely attributed to the promoter and not the viral serotype. We also report that a dual virus approach using an OXT promoter driven Cre recombinase significantly improved the efficiency of viral transduction in OXT neurons. Finally, we demonstrate the utility of the OXT promoter for conducting functional studies on OXT neurons by using an OXT specific viral system to record neural activity of OXT neurons in lactating female rats across time. We conclude that extreme caution is needed when employing non-neuron-specific viral approaches/promoters to study neural populations within the paraventricular nucleus of the hypothalamus.https://doi.org/10.1038/s41598-021-01818-x
spellingShingle Keerthi Thirtamara Rajamani
Amanda B. Leithead
Michelle Kim
Marie Barbier
Michael Peruggia
Kristi Niblo
Lara Barteczko
Arthur Lefevre
Valery Grinevich
Hala Harony-Nicolas
Efficiency of cell-type specific and generic promoters in transducing oxytocin neurons and monitoring their neural activity during lactation
Scientific Reports
title Efficiency of cell-type specific and generic promoters in transducing oxytocin neurons and monitoring their neural activity during lactation
title_full Efficiency of cell-type specific and generic promoters in transducing oxytocin neurons and monitoring their neural activity during lactation
title_fullStr Efficiency of cell-type specific and generic promoters in transducing oxytocin neurons and monitoring their neural activity during lactation
title_full_unstemmed Efficiency of cell-type specific and generic promoters in transducing oxytocin neurons and monitoring their neural activity during lactation
title_short Efficiency of cell-type specific and generic promoters in transducing oxytocin neurons and monitoring their neural activity during lactation
title_sort efficiency of cell type specific and generic promoters in transducing oxytocin neurons and monitoring their neural activity during lactation
url https://doi.org/10.1038/s41598-021-01818-x
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