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

Abstract

Angiotensin II acts via two main receptors within the central nervous system, with the type 1A receptor (ATR) most widely expressed in adult neurons. Activation of the ATR in the nucleus of the solitary tract (NTS), the principal nucleus receiving central synapses of viscerosensory afferents, modulates cardiovascular reflexes. Expression of the ATR occurs in high density within the NTS of most mammals, including humans, but the fundamental electrophysiological and neurochemical characteristics of the ATR-expressing NTS neurons are not known. To address this, we have used a transgenic mouse, in which the ATR promoter drives expression of green fluorescent protein (GFP). Approximately one-third of ATR-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 ATR-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, ATR-GFP neurons exhibited voltage-activated potassium currents, including the transient outward current and the M-type potassium current. In two different mouse strains, both ATR-GFP neurons and TH-GFP neurons showed similar ATR-mediated depolarizing responses to superfusion with angiotensin II. These data provide a comprehensive description of ATR-expressing neurons in the NTS and increase our understanding of the complex actions of this neuropeptide in the modulation of viscerosensory processing.

Viscerosensory input drives angiotensin II type 1A receptor-expressing neurons in the solitary tract nucleus

“…As some neurons received more than one visceral sensory input, we examined nine direct ST inputs onto seven second-order neurons (mean series resistance ϭ 14.35 Ϯ 3.18 M⍀). Previously, we have demonstrated that 2 M ANG II induces a 3-mV depolarization in AT 1A R-expressing NTS neurons (15). In the present study, ANG II application resulted in the development of an inward current, Ϫ6 Ϯ 1 pA (range from Ϫ1 to Ϫ10 pA) in each second-order neuron tested in 2 mM [Ca 2ϩ ] o (n ϭ 7, P Ͻ 0.05 Student's paired t-test).…”

“…Two-thirds of AT 1A R-expressing neurons receive direct visceral sensory inputs placing ANG II in a position to directly influence reception of visceral sensory information. Based on previous data (11,15), ANG II sensitizes NTS neurons to reception of sensory afferent information. Key to this conclusion, which is derived from our use of an ST recruitment protocol, is that ST-EPSCs which display high variability in synaptic latency involve interneurons between the stimulated visceral afferent and the recorded neuron.…”

“…Clearly some NTS neurochemical phenotypes, such as A2 neurons, are more likely to be second order, when compared with AT 1A R-expressing neurons. However, some A2 neurons express the AT 1A R (15,16,27), and this percentage of coexpression varies according to the subnucleus. Combined, these data indicate expression of the AT 1A R does not significantly differentiate the viscerosensory pathway to these NTS neuron, and AT 1A R-expressing neurons are likely to integrate direct and indirect sensory relays in the NTS.…”

“…Components of the renin-angiotensin system (RAS) are expressed within the NTS, including the angiotensin II (ANG II) type 1A receptor (AT 1A R), which is expressed in a subpopulation of NTS neurons and on the presynaptic terminals of some visceral sensory afferents (15,16,27,33). Dysregulation of the central RAS is implicated in many animal models of hypertension (17,30,44,59), which are also often accompanied by baroreflex desensitization or resetting (12,13,17,34).…”

Effects of acute and chronic nicotine on catecholamine neurons of the nucleus of the solitary tract

“…In contrast, CCK, oxytocin, ghrelin, serotonin, and opioids all control NTS neuronal activity indirectly through presynaptic modulation of glutamate release (2, 6, 15-17, 36, 43, 45, 69, 90). Interestingly, angiotensin II was also recently shown to have postsynaptic actions on NTS neurons (13), and oxytocin has postsynaptic actions in a subpopulation of NTS neurons (43,69).…”