Central Command Neurons of the Sympathetic Nervous System: Basis of the Fight-or-Flight Response.

Central Command Neurons of the Sympathetic Nervous System: Basis of the Fight-or-Flight Response. Arthur S. P. Jansen, Xay Van Nguyen, Vladimir Karpitskiy,Thomas C. Mettenleiter, Arthur D. Loewy. Science 270:644-646, 1995. This is a classic paper by Arthur Loewy's group at Washington University in St. Louis in which they propose the existence of "central command" neurons. These central command neurons are hypothesized to innervate multiple sympathetic targets and be responsible for the all or none, fight or flight response that has been traditionally associated with activation of the sympathetic nervous system. One thing to keep in mind here was that this paper was published in the mid-1990s when it was still controversial whether there were neurons that controlled some or all of the sympathetic outputs, whether there existed individual neurons that controlled individual sympathetic outputs, or if both types existed (likely the reality). Unlike the Australians (i.e. McAllen and colleagues), who had just the year prior shown differential control of sympathetic outputs with very small (5ul) microinjections in the RVLM of cats, Loewy's group was trying to demonstrate the reverse idea; that is, individual neurons have the anatomical connections to control multiple sympathetic outputs. To do so, they injected rats with two different viruses to produce retrograde and transynaptic tract tracing. They put one virus in the stellate ganglion which contains the axons of sympathetic preganglionics to the heart and they put a different virus in the adrenal gland which contains the sympathetic preganglionics controlling epinephrine release. While they did show that both viruses wound up within cells of the RVLM, there were several caveats pointed out in the paper and additional ones not pointed out. First, the number of cells that did show double labeling in the RVLM were very small and if you look in the Methods sections you will see it took them hundreds of rats to get this to work out. Second, there are several technical issues in using viruses that likely preclude definitive conclusions about the double-labeled cells. In any case, it was published in Science and is often quoted as the paper that demonstrated the existence of these neurons. It also propagates the still pervasive idea that sympathetics are an all or none phenomenon. We know now that this is not the case in several instances of physiology and pathophysiology. ~PJM