Angiotensin type 1A receptor expressing neurons in the NTS receive direct solitary tract excitatory neurotransmission

Abstract

Second order neurons in the nucleus of the solitary tract (NTS) receive direct viscero‐sensory afferents from internal organs via the solitary tract (ST) to coordinate autonomic reflexes. Approximately 90% ST vagal afferents from the heart and lungs are unmyelinated c‐fibres and express transient receptor potential vallinoid type 1 (TRPV1). Activation of the angiotensin type 1A receptor (AT1AR) in the NTS modulates cardiorespiratory reflexes and is thought to potentiate ST excitatory input. Here we aimed to characterise ST input to AT1AR expressing NTS neurons, and determine what proportion of the monosynaptic afferents express TPRV1. Second, we determined the impact of angiotensin II (AngII) on ST neurotransmission to AT1AR expressing NTS neurons. We employed in vitro slice electrophysiology and whole cell recordings. Twenty‐two transgenic mice expressing green fluorescent protein in AT1AR neurons were sacrificed and 250 μm horizontal brain stem slices were prepared and superfused with artificial cerebrospinal fluid. Electrical stimulation of the ST evoked low jitter excitatory post‐synaptic currents (ST‐EPSCs) in 28 of 41 GFP positive neurons, identifying them as second order. The normalised amplitude (eEPSC/eEPSCMAX) and paired pulse ration (PPR) of ST‐EPSCs (50 Hz, 200 μs) and frequency of spontaneous (F‐sEPSCs) and asynchronous EPSCs (F‐aEPSCs) were analysed before and during the addition of 100 nM capsaicin (CAP) or 2 μM AngII to the superfusate. CAP decreased F‐aEPSCs (CSF: 13.9 ± 2.3 Hz, CAP: 0.3 ± 2.7 Hz, n = 5), however only inhibited ST‐EPSCs in 1/5 second order neurons tested. AngII had no effect on ST‐EPSC amplitude (CSF: 0.84 ± 0.03, AngII: 0.85 ± 0.05), PPR (CSF: 0.34 ± 0.05, AngII: 0.34 ± 0.04, n = 8) or F‐sEPSC. Combined, this data indicates that NTS AT1AR neurons receive direct viscerosensory signals mostly via TRPV1‐ve pathways. Further, that AT1AR is not likely to be expressed on the excitatory ST axons/terminals contacting these AT1AR expressing NTS neurons. This suggests AT1AR neurons in the NTS receive predominately Aδ‐fibre input which relay high fidelity, low threshold signals from the viscera through the central nervous system.Support or Funding InformationThis work is supported by a National heart foundation post‐graduate research scholarship.