Functional and neurochemical characterization of angiotensin type 1A receptor-expressing neurons in the nucleus of the solitary tract of the mouse

Angiotensin II acts via two main receptors within the central nervous system, with the type 1A receptor (AT_1AR) most widely expressed in adult neurons. Activation of the AT₁R in the nucleus of the solitary tract (NTS), the principal nucleus receiving central synapses of viscerosensory afferents, modulates cardiovascular reflexes. Expression of the AT₁R occurs in high density within the NTS of most mammals, including humans, but the fundamental electrophysiological and neurochemical characteristics of the AT_1AR-expressing NTS neurons are not known. To address this, we have used a transgenic mouse, in which the AT_1AR promoter drives expression of green fluorescent protein (GFP). Approximately one-third of AT_1AR-expressing neurons express the catecholamine-synthetic enzyme tyrosine hydroxylase (TH), and a subpopulation of these stained for the transcription factor paired-like homeobox 2b (Phox2b). A third group, comprising approximately two-thirds of the AT_1AR-expressing NTS neurons, showed Phox2b immunoreactivity alone. A fourth group in the ventral subnucleus expressed neither TH nor Phox2b. In whole cell recordings from slices in vitro, AT_1AR-GFP neurons exhibited voltage-activated potassium currents, including the transient outward current and the M-type potassium current. In two different mouse strains, both AT_1AR-GFP neurons and TH-GFP neurons showed similar AT_1AR-mediated depolarizing responses to superfusion with angiotensin II. These data provide a comprehensive description of AT_1AR-expressing neurons in the NTS and increase our understanding of the complex actions of this neuropeptide in the modulation of viscerosensory processing.

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