The subfornical organ is the primary locus of sodium-level sensing by Nax sodium channels for the control of salt-intake behavior

Takeshi Y. Hiyama, Eiji Watanabe, Haruo Okado, Masaharu Noda

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

Dehydration causes an increase in the sodium (Na) concentration and osmolarity of body fluid. For Na homeostasis of the body, controls of Na and water intake and excretion are of prime importance. However, the system for sensing the Na level within the brain that is responsible for the control of Na- and water-intake behavior remains to be elucidated. We reported previously that the Nax channel is preferentially expressed in the circumventricular organs (CVOs) in the brain and that Nax knock-out mice ingest saline in excess under dehydrated conditions. Subsequently, we demonstrated that Nax is a Na-level-sensitive Na channel. Here we show that the subfornical organ (SFO) is the principal site for the control of salt-intake behavior, where the Nax channel is the Na-level sensor. Infusion of a hypertonic Na solution into the cerebral ventricle induced extensive water intake and aversion to saline in wild-type animals but not in the knock-out mice. Importantly, the aversion to salt was not induced by the infusion of a hyperosmotic mannitol solution with physiological Na concentration in either genotype of mice. When Nax cDNA was introduced into the brain of the knock-out mice with an adenoviral expression vector, only animals that received a transduction of the Nax gene into the SFO among the CVOs recovered salt-avoiding behavior under dehydrated conditions. These results clearly show that the SFO is the center of the control of salt-intake behavior in the brain, where the Na-level-sensitive Nax channel is involved in sensing the physiological increase in the Na level of body fluids.

Original languageEnglish
Pages (from-to)9276-9281
Number of pages6
JournalJournal of Neuroscience
Volume24
Issue number42
DOIs
Publication statusPublished - Oct 20 2004
Externally publishedYes

Fingerprint

Subfornical Organ
Sodium Channels
Salts
Sodium
Knockout Mice
Drinking
Brain
Body Fluids
Hypertonic Solutions
Cerebral Ventricles
Wild Animals
Mannitol
Dehydration
Osmolar Concentration
Homeostasis
Complementary DNA
Genotype
Genes
Circumventricular Organs

Keywords

  • Circumventricular organs
  • CSF
  • OVLT
  • Salt-intake behavior
  • SFO
  • Sodium channel

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

The subfornical organ is the primary locus of sodium-level sensing by Nax sodium channels for the control of salt-intake behavior. / Hiyama, Takeshi Y.; Watanabe, Eiji; Okado, Haruo; Noda, Masaharu.

In: Journal of Neuroscience, Vol. 24, No. 42, 20.10.2004, p. 9276-9281.

Research output: Contribution to journalArticle

@article{67bcff25a8284b4483c6fad1726633d1,
title = "The subfornical organ is the primary locus of sodium-level sensing by Nax sodium channels for the control of salt-intake behavior",
abstract = "Dehydration causes an increase in the sodium (Na) concentration and osmolarity of body fluid. For Na homeostasis of the body, controls of Na and water intake and excretion are of prime importance. However, the system for sensing the Na level within the brain that is responsible for the control of Na- and water-intake behavior remains to be elucidated. We reported previously that the Nax channel is preferentially expressed in the circumventricular organs (CVOs) in the brain and that Nax knock-out mice ingest saline in excess under dehydrated conditions. Subsequently, we demonstrated that Nax is a Na-level-sensitive Na channel. Here we show that the subfornical organ (SFO) is the principal site for the control of salt-intake behavior, where the Nax channel is the Na-level sensor. Infusion of a hypertonic Na solution into the cerebral ventricle induced extensive water intake and aversion to saline in wild-type animals but not in the knock-out mice. Importantly, the aversion to salt was not induced by the infusion of a hyperosmotic mannitol solution with physiological Na concentration in either genotype of mice. When Nax cDNA was introduced into the brain of the knock-out mice with an adenoviral expression vector, only animals that received a transduction of the Nax gene into the SFO among the CVOs recovered salt-avoiding behavior under dehydrated conditions. These results clearly show that the SFO is the center of the control of salt-intake behavior in the brain, where the Na-level-sensitive Nax channel is involved in sensing the physiological increase in the Na level of body fluids.",
keywords = "Circumventricular organs, CSF, OVLT, Salt-intake behavior, SFO, Sodium channel",
author = "Hiyama, {Takeshi Y.} and Eiji Watanabe and Haruo Okado and Masaharu Noda",
year = "2004",
month = "10",
day = "20",
doi = "10.1523/JNEUROSCI.2795-04.2004",
language = "English",
volume = "24",
pages = "9276--9281",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "42",

}

TY - JOUR

T1 - The subfornical organ is the primary locus of sodium-level sensing by Nax sodium channels for the control of salt-intake behavior

AU - Hiyama, Takeshi Y.

AU - Watanabe, Eiji

AU - Okado, Haruo

AU - Noda, Masaharu

PY - 2004/10/20

Y1 - 2004/10/20

N2 - Dehydration causes an increase in the sodium (Na) concentration and osmolarity of body fluid. For Na homeostasis of the body, controls of Na and water intake and excretion are of prime importance. However, the system for sensing the Na level within the brain that is responsible for the control of Na- and water-intake behavior remains to be elucidated. We reported previously that the Nax channel is preferentially expressed in the circumventricular organs (CVOs) in the brain and that Nax knock-out mice ingest saline in excess under dehydrated conditions. Subsequently, we demonstrated that Nax is a Na-level-sensitive Na channel. Here we show that the subfornical organ (SFO) is the principal site for the control of salt-intake behavior, where the Nax channel is the Na-level sensor. Infusion of a hypertonic Na solution into the cerebral ventricle induced extensive water intake and aversion to saline in wild-type animals but not in the knock-out mice. Importantly, the aversion to salt was not induced by the infusion of a hyperosmotic mannitol solution with physiological Na concentration in either genotype of mice. When Nax cDNA was introduced into the brain of the knock-out mice with an adenoviral expression vector, only animals that received a transduction of the Nax gene into the SFO among the CVOs recovered salt-avoiding behavior under dehydrated conditions. These results clearly show that the SFO is the center of the control of salt-intake behavior in the brain, where the Na-level-sensitive Nax channel is involved in sensing the physiological increase in the Na level of body fluids.

AB - Dehydration causes an increase in the sodium (Na) concentration and osmolarity of body fluid. For Na homeostasis of the body, controls of Na and water intake and excretion are of prime importance. However, the system for sensing the Na level within the brain that is responsible for the control of Na- and water-intake behavior remains to be elucidated. We reported previously that the Nax channel is preferentially expressed in the circumventricular organs (CVOs) in the brain and that Nax knock-out mice ingest saline in excess under dehydrated conditions. Subsequently, we demonstrated that Nax is a Na-level-sensitive Na channel. Here we show that the subfornical organ (SFO) is the principal site for the control of salt-intake behavior, where the Nax channel is the Na-level sensor. Infusion of a hypertonic Na solution into the cerebral ventricle induced extensive water intake and aversion to saline in wild-type animals but not in the knock-out mice. Importantly, the aversion to salt was not induced by the infusion of a hyperosmotic mannitol solution with physiological Na concentration in either genotype of mice. When Nax cDNA was introduced into the brain of the knock-out mice with an adenoviral expression vector, only animals that received a transduction of the Nax gene into the SFO among the CVOs recovered salt-avoiding behavior under dehydrated conditions. These results clearly show that the SFO is the center of the control of salt-intake behavior in the brain, where the Na-level-sensitive Nax channel is involved in sensing the physiological increase in the Na level of body fluids.

KW - Circumventricular organs

KW - CSF

KW - OVLT

KW - Salt-intake behavior

KW - SFO

KW - Sodium channel

UR - http://www.scopus.com/inward/record.url?scp=7044227669&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=7044227669&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.2795-04.2004

DO - 10.1523/JNEUROSCI.2795-04.2004

M3 - Article

C2 - 15496663

AN - SCOPUS:7044227669

VL - 24

SP - 9276

EP - 9281

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 42

ER -