Based on our earlier observations (Duale et al., 2007) and literature analysis (Kasparov & Teschemacher, 2008) we proposed that the A2 cell group, comprised of noradrenergic neurones within the nucleus tractus solitarii (NTS), is part of the central circuit which negatively controls arterial blood pressure. To further address this hypothesis we selectively activated and inhibited A2 neurones in vivo using lentiviral vector-driven transgene expression. Male Wistar rats were anaesthetised with a mixture of ketamine (60 mg/kg, i.m.) and medetomidine (250 μg/kg, i.m.) and bilaterally microinjected with lentiviral vectors into the NTS. Following surgery, animals were given post-operative care and housed normally for 3-6 weeks. They were then re-anaesthetised with urethane (1.15 – 1.4 g/kg, i.v.) and a craniotomy was performed in order to expose the dorsal surface of the brainstem. Mean arterial blood pressure (MABP) and heart rate (HR) were monitored. Selective viral vector-mediated transgene expression in A2 neurones was confirmed by immunohistochemical analysis post hoc. In order to selectively decrease activity of A2 neurones, we expressed an insect Gi-protein coupled receptor for the peptide ligand allatostatin (Alst; Lechner et al., 2002; vector: LVV.PRS8-AlstR-IRES-EGFP). Application of Alst (1 µM in aCSF) to the dorsal surface of the medulla resulted in significant increases in MABP by 12 ± 2 mm Hg (p = 0.003, n = 4; Student’s paired t-test) whilst HR remained unaffected (p = 0.2). For selective activation of A2 neurones we took an opto-genetic approach and expressed the algal light-sensitive cation channel channelrhodopsin-2 (vector: LVV.sIPRS8-hChR2(H134R)-EYFP). Flashing blue light (20 msec pulses; 50 Hz; 30 – 60 sec duration) was delivered by a 445 nm diode laser (Omicron, Germany) via a fibre-coupled optrode (conical shape manufactured from 400 μm core, ART Photonics, Germany). Power at the tip of the optrode was tuned to 15 – 18 mW. The optrode tip was placed above the dorsal medullary surface at different areas of the NTS. Preliminary experiments (n = 2 rats) showed transient, reversible and repeatable decreases in MABP by 12 ± 3 mm Hg with a latency of 3 ± 1 sec. Hypotension lasted for the period of stimulation and then gradually recovered (1 – 5 min). HR was not consistently changed. These observations are consistent with the hypothesis of an acute restraining influence of A2 neurones on arterial blood pressure, in line with their long-term actions which we described earlier. The mechanisms by which A2 neurones exert this effect require further investigation.