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

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 314; no. 2; pp. R282 - R293
• Main Authors: Carter, D A, Guo, H, Connelly, A A, Bassi, J K, Fong, A Y, Allen, A M, McDougall, S J
• Format: Journal Article
• Language: English
• Published: United States 01.02.2018
• Subjects: Angiotensin II - pharmacology; Animals; Genes, Reporter; Glutamic Acid - metabolism; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Membrane Potentials; Mice, Transgenic; Nerve Fibers, Myelinated - metabolism; Nerve Fibers, Unmyelinated - metabolism; Neurons, Afferent - drug effects; Neurons, Afferent - metabolism; Promoter Regions, Genetic; Receptor, Angiotensin, Type 1 - agonists; Receptor, Angiotensin, Type 1 - genetics; Receptor, Angiotensin, Type 1 - metabolism; Solitary Nucleus - cytology; Solitary Nucleus - drug effects; Solitary Nucleus - metabolism; Synaptic Transmission; visceral; NTS; sensory; vagus; nodose
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00290.2017

Homeostatic regulation of visceral organ function requires integrated processing of neural and neurohormonal sensory signals. The nucleus of the solitary tract (NTS) is the primary sensory nucleus for cranial visceral sensory afferents. Angiotensin II (ANG II) is known to modulate peripheral visceral reflexes, in part, by activating ANG II type 1A receptors (AT R) in the NTS. AT R-expressing NTS neurons occur throughout the NTS with a defined subnuclear distribution, and most of these neurons are depolarized by ANG II. In this study we determined whether AT R-expressing NTS neurons receive direct visceral sensory input, and whether this input is modulated by ANG II. Using AT R-GFP mice to make targeted whole cell recordings from AT R-expressing NTS neurons, we demonstrate that two-thirds (37 of 56) of AT R-expressing neurons receive direct excitatory, visceral sensory input. In half of the neurons tested (4 of 8) the excitatory visceral sensory input was significantly reduced by application of the transient receptor potential vallinoid type 1 receptor agonist, capsaicin, indicating AT R-expressing neurons can receive either C- or A-fiber-mediated input. Application of ANG II to a subset of second-order AT R-expressing neurons did not affect spontaneous, evoked, or asynchronous glutamate release from visceral sensory afferents. Thus it is unlikely that AT R-expressing viscerosensory neurons terminate on AT R-expressing NTS neurons. Our data suggest that ANG II is likely to modulate multiple visceral sensory modalities by altering the excitability of second-order AT R-expressing NTS neurons.