Identification of substances which regulate activity of corticotropin-releasing factor-producing neurons in the paraventricular nucleus of the hypothalamus

Abstract The stress response is a physiological system for adapting to various internal and external stimuli. Corticotropin-releasing factor-producing neurons in the paraventricular nucleus of the hypothalamus (PVN-CRF neurons) are known to play an important role in the stress response as initiators...

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Autores principales:	Yasutaka Mukai, Ayako Nagayama, Keiichi Itoi, Akihiro Yamanaka
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/89abc7a6d9254ad28d078625cb9f0721
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spelling	oai:doaj.org-article:89abc7a6d9254ad28d078625cb9f07212021-12-02T18:50:49ZIdentification of substances which regulate activity of corticotropin-releasing factor-producing neurons in the paraventricular nucleus of the hypothalamus10.1038/s41598-020-70481-52045-2322https://doaj.org/article/89abc7a6d9254ad28d078625cb9f07212020-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-70481-5https://doaj.org/toc/2045-2322Abstract The stress response is a physiological system for adapting to various internal and external stimuli. Corticotropin-releasing factor-producing neurons in the paraventricular nucleus of the hypothalamus (PVN-CRF neurons) are known to play an important role in the stress response as initiators of the hypothalamic–pituitary–adrenal axis. However, the mechanism by which activity of PVN-CRF neurons is regulated by other neurons and bioactive substances remains unclear. Here, we developed a screening method using calcium imaging to identify how physiological substances directly affect the activity of PVN-CRF neurons. We used acute brain slices expressing a genetically encoded calcium indicator in PVN-CRF neurons using CRF-Cre recombinase mice and an adeno-associated viral vector under Cre control. PVN-CRF neurons were divided into ventral and dorsal portions. Bath application of candidate substances revealed 12 substances that increased and 3 that decreased intracellular calcium concentrations. Among these substances, angiotensin II and histamine mainly increased calcium in the ventral portion of the PVN-CRF neurons via AT1 and H1 receptors, respectively. Conversely, carbachol mainly increased calcium in the dorsal portion of the PVN-CRF neurons via both nicotinic and muscarinic acetylcholine receptors. Our method provides a precise and reliable means of evaluating the effect of a substance on PVN-CRF neuronal activity.Yasutaka MukaiAyako NagayamaKeiichi ItoiAkihiro YamanakaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-14 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yasutaka Mukai Ayako Nagayama Keiichi Itoi Akihiro Yamanaka Identification of substances which regulate activity of corticotropin-releasing factor-producing neurons in the paraventricular nucleus of the hypothalamus
description	Abstract The stress response is a physiological system for adapting to various internal and external stimuli. Corticotropin-releasing factor-producing neurons in the paraventricular nucleus of the hypothalamus (PVN-CRF neurons) are known to play an important role in the stress response as initiators of the hypothalamic–pituitary–adrenal axis. However, the mechanism by which activity of PVN-CRF neurons is regulated by other neurons and bioactive substances remains unclear. Here, we developed a screening method using calcium imaging to identify how physiological substances directly affect the activity of PVN-CRF neurons. We used acute brain slices expressing a genetically encoded calcium indicator in PVN-CRF neurons using CRF-Cre recombinase mice and an adeno-associated viral vector under Cre control. PVN-CRF neurons were divided into ventral and dorsal portions. Bath application of candidate substances revealed 12 substances that increased and 3 that decreased intracellular calcium concentrations. Among these substances, angiotensin II and histamine mainly increased calcium in the ventral portion of the PVN-CRF neurons via AT1 and H1 receptors, respectively. Conversely, carbachol mainly increased calcium in the dorsal portion of the PVN-CRF neurons via both nicotinic and muscarinic acetylcholine receptors. Our method provides a precise and reliable means of evaluating the effect of a substance on PVN-CRF neuronal activity.
format	article
author	Yasutaka Mukai Ayako Nagayama Keiichi Itoi Akihiro Yamanaka
author_facet	Yasutaka Mukai Ayako Nagayama Keiichi Itoi Akihiro Yamanaka
author_sort	Yasutaka Mukai
title	Identification of substances which regulate activity of corticotropin-releasing factor-producing neurons in the paraventricular nucleus of the hypothalamus
title_short	Identification of substances which regulate activity of corticotropin-releasing factor-producing neurons in the paraventricular nucleus of the hypothalamus
title_full	Identification of substances which regulate activity of corticotropin-releasing factor-producing neurons in the paraventricular nucleus of the hypothalamus
title_fullStr	Identification of substances which regulate activity of corticotropin-releasing factor-producing neurons in the paraventricular nucleus of the hypothalamus
title_full_unstemmed	Identification of substances which regulate activity of corticotropin-releasing factor-producing neurons in the paraventricular nucleus of the hypothalamus
title_sort	identification of substances which regulate activity of corticotropin-releasing factor-producing neurons in the paraventricular nucleus of the hypothalamus
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/89abc7a6d9254ad28d078625cb9f0721
work_keys_str_mv	AT yasutakamukai identificationofsubstanceswhichregulateactivityofcorticotropinreleasingfactorproducingneuronsintheparaventricularnucleusofthehypothalamus AT ayakonagayama identificationofsubstanceswhichregulateactivityofcorticotropinreleasingfactorproducingneuronsintheparaventricularnucleusofthehypothalamus AT keiichiitoi identificationofsubstanceswhichregulateactivityofcorticotropinreleasingfactorproducingneuronsintheparaventricularnucleusofthehypothalamus AT akihiroyamanaka identificationofsubstanceswhichregulateactivityofcorticotropinreleasingfactorproducingneuronsintheparaventricularnucleusofthehypothalamus
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Identification of substances which regulate activity of corticotropin-releasing factor-producing neurons in the paraventricular nucleus of the hypothalamus

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