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

Jon M Resch; Henning Fenselau; Joseph C Madara; Chen Wu; John N Campbell; Anna Lyubetskaya; Brian A Dawes; Linus T Tsai; Monica M Li; Yoav Livneh; Qingen Ke; Peter M Kang; Géza Fejes-Tóth; Anikó Náray-Fejes-Tóth; Joel C Geerling; Bradford B Lowell

doi:10.1016/j.neuron.2017.09.014

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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

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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

Jon M Resch, Henning Fenselau, Joseph C Madara, Chen Wu, John N Campbell, Anna Lyubetskaya, Brian A Dawes, Linus T Tsai, Monica M Li, Yoav Livneh, …

Neuron (Cambridge, Mass.), Vol.96(1), pp.190-206.e7

09/27/2017

DOI: 10.1016/j.neuron.2017.09.014

PMCID: PMC5637454

PMID: 28957668

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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 (NTS neurons) were shown to drive sodium appetite. Here we investigate the basis for NTS neuron activation, identify the circuit by which NTS neurons drive appetite, and uncover an interaction between the NTS circuit and ATII signaling. NTS neurons respond to sodium deficiency with spontaneous pacemaker-like activity-the consequence of "cardiac" HCN and Na 1.5 channels. Remarkably, NTS neurons are necessary for sodium appetite, and with concurrent ATII signaling their activity is sufficient to produce rapid consumption. Importantly, NTS 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 NTS neurons provides a neuronal context for the long-standing "synergy hypothesis" of sodium appetite regulation.

Signal Transduction

Aldosterone - physiology

Septal Nuclei - physiology

Male

Mice, Transgenic

NAV1.5 Voltage-Gated Sodium Channel - physiology

Neural Pathways - physiology

Eating - physiology

Sodium - deficiency

Solitary Nucleus - physiology

Animals

Biological Clocks - physiology

Neurons - physiology

Mice

Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels - physiology

Sodium - physiology

Angiotensin II - physiology

Details

Title: Subtitle: Aldosterone-Sensing Neurons in the NTS Exhibit State-Dependent Pacemaker Activity and Drive Sodium Appetite via Synergy with Angiotensin II Signaling
Creators: Jon M Resch - Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Henning Fenselau - Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Joseph C Madara - Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Chen Wu - Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
John N Campbell - Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Anna Lyubetskaya - Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Brian A Dawes - Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Linus T Tsai - Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Monica M Li - Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Yoav Livneh - Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Qingen Ke - Cardiovascular Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Peter M Kang - Cardiovascular Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Géza Fejes-Tóth - Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03755, USA
Anikó Náray-Fejes-Tóth - Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03755, USA
Joel C Geerling - Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Electronic address: joel-geerling@uiowa.edu
Bradford B Lowell - Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA. Electronic address: blowell@bidmc.harvard.edu
Resource Type: Journal article
Publication Details: Neuron (Cambridge, Mass.), Vol.96(1), pp.190-206.e7
Publisher: United States
DOI: 10.1016/j.neuron.2017.09.014
PMID: 28957668
PMCID: PMC5637454
ISSN: 0896-6273
eISSN: 1097-4199
Grant note: R01 DK096010 / NIDDK NIH HHS R01 DK111401 / NIDDK NIH HHS R01 DK089044 / NIDDK NIH HHS R01 DK075632 / NIDDK NIH HHS F32 DK103387 / NIDDK NIH HHS P30 DK046200 / NIDDK NIH HHS K08 NS099425 / NINDS NIH HHS P30 DK057521 / NIDDK NIH HHS
Language: English
Date published: 09/27/2017
Academic Unit: Neurology; Iowa Neuroscience Institute; Neuroscience and Pharmacology
Record Identifier: 9984020644302771

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