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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.

Neuron | Sep 27, 2017

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.

Pubmed ID: 28957668 RIS Download

Mesh terms: Aldosterone | Angiotensin II | Animals | Biological Clocks | Eating | Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels | Male | Mice | Mice, Transgenic | NAV1.5 Voltage-Gated Sodium Channel | Neural Pathways | Neurons | Septal Nuclei | Signal Transduction | Sodium | Solitary Nucleus

Data used in this publication

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Associated grants

  • Agency: NIDDK NIH HHS, Id: R01 DK089044
  • Agency: NIDDK NIH HHS, Id: R01 DK096010
  • Agency: NIDDK NIH HHS, Id: P30 DK046200
  • Agency: NINDS NIH HHS, Id: K08 NS099425
  • Agency: NIDDK NIH HHS, Id: P30 DK057521
  • Agency: NIDDK NIH HHS, Id: R01 DK075632
  • Agency: NIDDK NIH HHS, Id: R01 DK111401
  • Agency: NIDDK NIH HHS, Id: F32 DK103387

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