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

Abstract

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 Ca2+ 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.

Central regulation of body fluid homeostasis

“…When AAV-DIO-mCherry was stereotaxically injected into the SFO of CCK-Cre mice, mCherry-positive cells in the SFO (CCK-positive cells) overlapped with nNOS-immunoreactive cells, indicating that they belong to excitatory neurons in the SFO. 138 ) The findings of qPCR also revealed significantly higher CCK mRNA levels (∼2.1-fold) in the SFO in Na-depleted conditions than in control conditions, suggesting the up-regulation of CCK in CCK-positive neurons in the SFO. 138 )…”

“…To clarify the location of CCK-producing cells, we measured CCK concentration ([CCK]) in blood and SFO tissues in water- and Na-depleted conditions. 138 ) Plasma [CCK] remained unchanged between the different conditions, whereas [CCK] in the SFO was markedly higher in Na-depleted conditions than in control conditions (∼9.0-fold). When AAV-DIO-mCherry was stereotaxically injected into the SFO of CCK-Cre mice, mCherry-positive cells in the SFO (CCK-positive cells) overlapped with nNOS-immunoreactive cells, indicating that they belong to excitatory neurons in the SFO.…”

“… 137 ) Water intake decreased from 1.33 ± 0.06 mL to 0.87 ± 0.09 mL in 30 min after the direct injection of a sulfated octapeptide of CCK into the SFO in water-depleted conditions. 138 )…”

Gliotransmission of D-serine promotes thirst-directed behaviors inDrosophila

“…Water deprivation reduces the volume and increases the osmolality of an animal’s hemolymph or blood. These changes induce multiple adaptations throughout the body, such as changes in the activity of osmosensory nuclei in the brain (the LT in mammals and ISNs in Drosophila ) as well as production and release of neuropeptide or neurohormone modulators (Augustine et al, 2020; Gáliková et al, 2018; Jourjine et al, 2016; Landayan et al, 2021; Matsuda et al, 2020; Senapati et al, 2019; Zimmerman et al, 2017). These molecules modulate organs controlling water retention, excretion and blood pressure, and the activity of neuronal circuits.…”

Neural basis for regulation of vasopressin secretion by anticipated disturbances in osmolality

“…Recent studies have identified multiple molecularly-or anatomically-distinct neuronal populations in the LT that are involved in different aspects of water homeostasis (Oka et al, 2015b;Abbott et al, 2016;Allen et al, 2017;Matsuda et al, 2017;Augustine et al, 2018;Matsuda et al, 2020;Pool et al, 2020). In this study, we investigated the role of the LT neurons in mediating presystemic regulation of AVP neurons.…”