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Clarification of the control mechanisms that prevent excessive water and salt intake — Neurons provide feedback control: Potential to contribute to treatment of polydipsia and other disorders


Water and salt are essential for sustaining life in vertebrates, including humans, but can cause various diseases of and fatal damage to the brain and other organs if they are consumed excessively. Water/salt-intake behavior is known to be controlled by the organum vasculosum of the lamina terminalis (OVLT) and the subfornical organ (SFO) in the brain, which lack a blood-brain barrier and monitor fluid status. It has also been known that thirst and salt appetite are temporarily suppressed with the intake of water and salt, but the detailed mechanisms were yet to be clarified.

A research group led by Specially Appointed Assistant Professor Takashi Matsuda and Specially Appointed Professor Masaharu Noda of the Institute of Innovative Research at Tokyo Institute of Technology, has found two distinct excitatory neuronal populations in the lateral parabrachial nucleus (LPBN) located between the midbrain and medulla oblongata the brain, and showed that one of the two populations was responsive to water intake signals from the digestive tract while the other was responsive to salt intake signals from the tongue. Next, they explored the pathways that transmit water and salt intake signals in the brain and found that the pathways leading to the median preoptic nucleus in the hypothalamus and the ventral part of the bed nucleus of the stria terminalis from the LPBN specifically inhibit water intake and salt intake, respectively. They found that signals from the LPBN were relayed to the inhibitory neurons of their respective terminals, and activation of these cells results in inhibition of water/salt-intake behavior. Regarding the inhibition of water intake, an excitatory neuronal population responsive to water intake was also found in the SFO, indicating that the SFO and LPBN are jointly responsible for the inhibitory control of water intake.

This clarification of basic brain mechanisms involved in the maintenance of life is expected to be useful for the treatment, prevention, and clarification of the etiology of diseases caused by excessive water and salt intake, such as water intoxication, polydipsia, and salt-sensitive hypertension.

Overview of the neural circuitry to inhibit water and salt intake. The yellow and red signaling mechanisms were discovered in this study (GABA is inhibitory, CCK is excitatory).

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