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

First Author  Mukai Y Year  2020
Journal  Sci Rep Volume  10
Issue  1 Pages  13639
PubMed ID  32788592 Mgi Jnum  J:299280
Mgi Id  MGI:6457766 Doi  10.1038/s41598-020-70481-5
Citation  Mukai Y, et al. (2020) Identification of substances which regulate activity of corticotropin-releasing factor-producing neurons in the paraventricular nucleus of the hypothalamus. Sci Rep 10(1):13639
abstractText  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.
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