Optimization of whole-brain rabies virus tracing technology for small cell populations

Abstract The lateral hypothalamus (LH) is critically involved in the regulation of homeostatic energy balance. Some neurons in the LH express receptors for leptin (LepRb), a hormone known to increase energy expenditure and decrease energy intake. However, the neuroanatomical inputs to LepRb-expressi...

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Autores principales:	Theresia J. M. Roelofs, Shanice Menting-Henry, Lieke M. Gol, Annelijn M. Speel, Vera H. Wielenga, Keith M. Garner, Mieneke C. M. Luijendijk, Alexandru A. Hennrich, Karl-Klaus Conzelmann, Roger A. H. Adan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/793b513311984bcbaeb6246069be3a08
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spelling	oai:doaj.org-article:793b513311984bcbaeb6246069be3a082021-12-02T14:58:32ZOptimization of whole-brain rabies virus tracing technology for small cell populations10.1038/s41598-021-89862-52045-2322https://doaj.org/article/793b513311984bcbaeb6246069be3a082021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89862-5https://doaj.org/toc/2045-2322Abstract The lateral hypothalamus (LH) is critically involved in the regulation of homeostatic energy balance. Some neurons in the LH express receptors for leptin (LepRb), a hormone known to increase energy expenditure and decrease energy intake. However, the neuroanatomical inputs to LepRb-expressing LH neurons remain unknown. We used rabies virus tracing technology to map these inputs, but encountered non-specific tracing. To optimize this technology for a minor cell population (LepRb is not ubiquitously expressed in LH), we used LepRb-Cre mice and assessed how different titers of the avian tumor virus receptor A (TVA) helper virus affected rabies tracing efficiency and specificity. We found that rabies expression is dependent on TVA receptor expression, and that leakiness of TVA receptors is dependent on the titer of TVA virus used. We concluded that a titer of 1.0–3.0 × 107 genomic copies per µl of the TVA virus is optimal for rabies tracing. Next, we successfully applied modified rabies virus tracing technology to map inputs to LepRb-expressing LH neurons. We discovered that other neurons in the LH itself, the periventricular hypothalamic nucleus (Pe), the posterior hypothalamic nucleus (PH), the bed nucleus of the stria terminalis (BNST), and the paraventricular hypothalamic nucleus (PVN) are the most prominent input areas to LepRb-expressing LH neurons.Theresia J. M. RoelofsShanice Menting-HenryLieke M. GolAnnelijn M. SpeelVera H. WielengaKeith M. GarnerMieneke C. M. LuijendijkAlexandru A. HennrichKarl-Klaus ConzelmannRoger A. H. AdanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Theresia J. M. Roelofs Shanice Menting-Henry Lieke M. Gol Annelijn M. Speel Vera H. Wielenga Keith M. Garner Mieneke C. M. Luijendijk Alexandru A. Hennrich Karl-Klaus Conzelmann Roger A. H. Adan Optimization of whole-brain rabies virus tracing technology for small cell populations
description	Abstract The lateral hypothalamus (LH) is critically involved in the regulation of homeostatic energy balance. Some neurons in the LH express receptors for leptin (LepRb), a hormone known to increase energy expenditure and decrease energy intake. However, the neuroanatomical inputs to LepRb-expressing LH neurons remain unknown. We used rabies virus tracing technology to map these inputs, but encountered non-specific tracing. To optimize this technology for a minor cell population (LepRb is not ubiquitously expressed in LH), we used LepRb-Cre mice and assessed how different titers of the avian tumor virus receptor A (TVA) helper virus affected rabies tracing efficiency and specificity. We found that rabies expression is dependent on TVA receptor expression, and that leakiness of TVA receptors is dependent on the titer of TVA virus used. We concluded that a titer of 1.0–3.0 × 107 genomic copies per µl of the TVA virus is optimal for rabies tracing. Next, we successfully applied modified rabies virus tracing technology to map inputs to LepRb-expressing LH neurons. We discovered that other neurons in the LH itself, the periventricular hypothalamic nucleus (Pe), the posterior hypothalamic nucleus (PH), the bed nucleus of the stria terminalis (BNST), and the paraventricular hypothalamic nucleus (PVN) are the most prominent input areas to LepRb-expressing LH neurons.
format	article
author	Theresia J. M. Roelofs Shanice Menting-Henry Lieke M. Gol Annelijn M. Speel Vera H. Wielenga Keith M. Garner Mieneke C. M. Luijendijk Alexandru A. Hennrich Karl-Klaus Conzelmann Roger A. H. Adan
author_facet	Theresia J. M. Roelofs Shanice Menting-Henry Lieke M. Gol Annelijn M. Speel Vera H. Wielenga Keith M. Garner Mieneke C. M. Luijendijk Alexandru A. Hennrich Karl-Klaus Conzelmann Roger A. H. Adan
author_sort	Theresia J. M. Roelofs
title	Optimization of whole-brain rabies virus tracing technology for small cell populations
title_short	Optimization of whole-brain rabies virus tracing technology for small cell populations
title_full	Optimization of whole-brain rabies virus tracing technology for small cell populations
title_fullStr	Optimization of whole-brain rabies virus tracing technology for small cell populations
title_full_unstemmed	Optimization of whole-brain rabies virus tracing technology for small cell populations
title_sort	optimization of whole-brain rabies virus tracing technology for small cell populations
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/793b513311984bcbaeb6246069be3a08
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Optimization of whole-brain rabies virus tracing technology for small cell populations

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