@article{e21d8846eb7d4ae5989d64c4a902743c,
title = "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.",
author = "Resch, \{Jon M.\} and Henning Fenselau and Madara, \{Joseph C.\} and Chen Wu and Campbell, \{John N.\} and Anna Lyubetskaya and Dawes, \{Brian A.\} and Tsai, \{Linus T.\} and Li, \{Monica M.\} and Yoav Livneh and Qingen Ke and Kang, \{Peter M.\} and G{\'e}za Fejes-T{\'o}th and Anik{\'o} N{\'a}ray-Fejes-T{\'o}th and Geerling, \{Joel C.\} and Lowell, \{Bradford B.\}",
note = "We would like to thank Dr. B. Bean for advice regarding electrophysiology experiments and pacemaker neurons; Drs. S. Liberles and D. Strochlic for helpful discussions and technical assistance regarding nodose ganglia experiments; Drs. M. Zeidel and M. Andermann and the Lowell laboratory for helpful discussions; C. Jacobs and the BNORC Functional Genomics and Bioinformatics core for helpful discussions and technical assistance; Y. Li, Z. Yang, and J. Yu for technical assistance; and the BIDMC Molecular Medicine Core for technical assistance. This research was funded by the following NIH grants to B.B.L.: R01 DK075632 , R01 DK096010 , R01 DK089044 , R01 DK111401 , P30 DK046200 , P30 DK057521 ; to J.C.G.: K08 NS099425 ; to J.M.R.: F32 DK103387 . J.N.C. was supported by an AHA Postdoctoral Fellowship ( 14POST20100011 ), and Y.L. was supported by an EMBO postdoctoral fellowship ( ALTF 408-2014 ). Author contributions - Conceptualization, J.M.R., H.F., J.C.G., and B.B.L.; Methodology, J.M.R., H.F., J.C.M., J.N.C., A.L., M.M.L., J.C.G., and B.B.L.; Validation, J.M.R, H.F., J.C.M., and C.W.; Formal Analysis; J.M.R., H.F., J.C.M., J.N.C., A.L., B.A.D., and L.T.T.; Investigation, J.M.R., H.F., J.C.M., C.W., J.N.C., Q.K., and J.C.G.; Resources, P.M.K., G.F.-T., A.N.-F.-T., and B.B.L.; Writing – Original Draft, J.M.R., J.C.G., and B.B.L.; Writing – Review \& Editing, J.M.R., H.F., J.C.M., J.N.C., Y.L., J.C.G., and B.B.L.; Funding Acquisition, J.M.R. and B.B.L.",
year = "2017",
month = sep,
day = "27",
doi = "10.1016/j.neuron.2017.09.014",
language = "الإنجليزيّة",
volume = "96",
pages = "190--206",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "1",
}