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Aldosterone-Sensing Neurons in the NTS Exhibit State-Dependent Pacemaker Activity and Drive Sodium Appetite via Synergy with Angiotensin II Signaling.


ABSTRACT: Sodium deficiency increases angiotensin II (ATII) and aldosterone, which synergistically stimulate sodium retention and consumption. Recently, ATII-responsive neurons in the subfornical organ (SFO) and aldosterone-sensitive neurons in the nucleus of the solitary tract (NTSHSD2 neurons) were shown to drive sodium appetite. Here we investigate the basis for NTSHSD2 neuron activation, identify the circuit by which NTSHSD2 neurons drive appetite, and uncover an interaction between the NTSHSD2 circuit and ATII signaling. NTSHSD2 neurons respond to sodium deficiency with spontaneous pacemaker-like activity-the consequence of "cardiac" HCN and Nav1.5 channels. Remarkably, NTSHSD2 neurons are necessary for sodium appetite, and with concurrent ATII signaling their activity is sufficient to produce rapid consumption. Importantly, NTSHSD2 neurons stimulate appetite via projections to the vlBNST, which is also the effector site for ATII-responsive SFO neurons. The interaction between angiotensin signaling and NTSHSD2 neurons provides a neuronal context for the long-standing "synergy hypothesis" of sodium appetite regulation.

SUBMITTER: Resch JM 

PROVIDER: S-EPMC5637454 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Aldosterone-Sensing Neurons in the NTS Exhibit State-Dependent Pacemaker Activity and Drive Sodium Appetite via Synergy with Angiotensin II Signaling.

Resch Jon M JM   Fenselau Henning H   Madara Joseph C JC   Wu Chen C   Campbell John N JN   Lyubetskaya Anna A   Dawes Brian A BA   Tsai Linus T LT   Li Monica M MM   Livneh Yoav Y   Ke Qingen Q   Kang Peter M PM   Fejes-Tóth Géza G   Náray-Fejes-Tóth Anikó A   Geerling Joel C JC   Lowell Bradford B BB  

Neuron 20170901 1


Sodium deficiency increases angiotensin II (ATII) and aldosterone, which synergistically stimulate sodium retention and consumption. Recently, ATII-responsive neurons in the subfornical organ (SFO) and aldosterone-sensitive neurons in the nucleus of the solitary tract (NTS<sup>HSD2</sup> neurons) were shown to drive sodium appetite. Here we investigate the basis for NTS<sup>HSD2</sup> neuron activation, identify the circuit by which NTS<sup>HSD2</sup> neurons drive appetite, and uncover an inter  ...[more]

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