Regulation of visceral sympathetic tone by A5 noradrenergic neurons in rodents.

Kanbar R, Depuy SD, West GH, Stornetta RL, Guyenet PG.

J Physiol. 2011 Feb 15;589(Pt 4):903-17

We’re pretty focused on the RVLM, but we know it’s not the only region of the brain that controls the same things we study. In this paper they looked at the A5 region, which also has spinal projections that go to IML. It has long been implicated in regulation of the autonomic system and respiration In fact, this function of the A5 has been suspected  since 1982. The cells here have been shown to have slow regular resting discharge, activated by nociceptive stimuli, inhibited by A2 agonists, activated by hypoxia and show respiratory modulation, but seem to be unaffected by changes in BP. The problem with pinpointing these effects was that there aren’t many A5 cells and they’re scattered around a small area that is surrounded by other areas that would affect nerve activity – this means microinjection studies were very hard to conduct, and A5’s effect on the control of SNA and blood pressure was difficult to establish. In this paper, they used an optogenetic approach (PRSX8-ChR2 again), combined with electrophysiology (including antidromic action potentials in the spinal cord) and juxtacellular labeling (along with immunology/TH staining), to isolate the cells of the A5 and see how they contribute to SNA.

They found 2 main types of neurons in the A5 region – the first group never showed antidromic action potential and had a huge response to increases in CO2. These cells were the most caudal and ventral ones, indicating that they were actually RTN cells living at the A5/RTN border. The other type were slow firing (<1Hz) bulbospinal ones that slightly increased activity with increasing CO2, or had no response. They were strongly activated by chemoreceptor activation (with cyanide). 4 out of 10 that they recorded were pulse modulated. Through juxtacellular labeling and immuno, these cells were shown to be TH positive, and optogenetic activation of these cells caused an increase in renal SNA (but had a very small effect on lumbar SNA). The cool thing about this paper was that they were able to combine old and new techniques to get a lot of information that would not have been possible through any of the individual techniques alone. -DH