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

Takashi Matsuda,Masaharu Noda,Takeshi Y Hiyama,Kenta Kobayashi,Kazuto Kobayashi

doi:10.1038/s41467-020-19191-0

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.

Highlights

The control of water-intake behavior is critical for life because an excessive water intake induces pathological conditions, such as hyponatremia or water intoxication
We demonstrated that an increase in plasma angiotensin II (Ang II) levels caused by dehydration or salt depletion was sensed by Ang II receptor 1a (AT1a) in water neurons and salt neurons, respectively[25]
We showed that the activity of water neurons in the subfornical organ (SFO) was suppressed by GABAergic neurons under Na-depleted conditions in a manner that was dependent on cholecystokinin (CCK)[25]; the CCK-mediated neural mechanisms underlying the inhibitory control of water intake have not yet been elucidated in detail

Summary

Introduction

The control of water-intake behavior is critical for life because an excessive water intake induces pathological conditions, such as hyponatremia or water intoxication. Increased sodium levels ([Na+]) in body fluids caused by the over-ingestion of salt worsens the prognosis of cardiovascular diseases, such as hypertension[5] and cardiac failure[6,7] These pathological conditions of body fluids lead to irreversible damage to organs, including the nervous system[8,9,10]. We showed that the activity of water neurons in the SFO was suppressed by GABAergic neurons under Na-depleted conditions in a manner that was dependent on cholecystokinin (CCK)[25]; the CCK-mediated neural mechanisms underlying the inhibitory control of water intake have not yet been elucidated in detail. CCK is intimately involved in a number of normal behaviors, such as learning, memory, feeding, nociception, and satiety[29]

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Results

Conclusion