Distinct CCK-positive SFO neurons are involved in persistent or transient suppression of water intake

• Published in: Nature communications Vol. 11; no. 1; p. 5692
• Main Authors: Matsuda, Takashi, Hiyama, Takeshi Y., Kobayashi, Kenta, Kobayashi, Kazuto, Noda, Masaharu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.11.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 14; 14/1; 14/19; 38/77; 631/378; 631/443; 631/443/319/1557; Behavior; Body fluids; Brain; Brain research; Calcium imaging; Calcium ions; Central nervous system; Cholecystokinin; Drinking water; Fluorescence; Humanities and Social Sciences; Hyponatremia; Interneurons; Intoxication; multidisciplinary; Neuroimaging; Neurons; Neurosciences; Physiology; Salt; Science; Science (multidisciplinary); Subfornical organ; Subpopulations; Thirst; Water intake; Water intakes; γ-Aminobutyric acid
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-19191-0

The control of water-intake behavior is critical for life because an excessive water intake induces pathological conditions, such as hyponatremia or water intoxication. However, the brain mechanisms controlling water intake currently remain unclear. We previously reported that thirst-driving neurons (water neurons) in the subfornical organ (SFO) are cholecystokinin (CCK)-dependently suppressed by GABAergic interneurons under Na-depleted conditions. We herein show that CCK-producing excitatory neurons in the SFO stimulate the activity of GABAergic interneurons via CCK-B receptors. Fluorescence-microscopic Ca 2+ imaging demonstrates two distinct subpopulations in CCK-positive neurons in the SFO, which are persistently activated under hyponatremic conditions or transiently activated in response to water drinking, respectively. Optical and chemogenetic silencings of the respective types of CCK-positive neurons both significantly increase water intake under water-repleted conditions. The present study thus reveals CCK-mediated neural mechanisms in the central nervous system for the control of water-intake behaviors. Water intake is critical to our life, and the subfornical organ in the brain involved in the control of this behavior. Here, the authors reveal that two distinct groups of CCK-producing neurons in the SFO suppress water intake according to the physiological condition or water-intake stimulus.