Vesicular glutamate transporter 2 is required for the respiratory and parasympathetic activation produced by optogenetic stimulation of catecholaminergic neurons in the rostral ventrolateral medulla of mice in vivo

Full cite: Abbott, S.B., Holloway, B.B., Viar, K.E. & Guyenet, P.G. (2013)Vesicular glutamate transporter 2 is required for the respiratory and parasympathetic activation produced by optogenetic stimulation of catecholaminergic neurons in the rostral ventrolateral medulla of mice in vivo. Eur. J. Neurosci., 39, 98-106. Stephen B. G. Abbott,1 Benjamin B. Holloway,1 Kenneth E. Viar1 and Patrice G. Guyenet1,2 1Department of Pharmacology, University of Virginia, Charlottesville, VA, USA 2University of Virginia Health System, P.O. Box 800735, 1300 Jefferson Park Avenue, Charlottesville, VA 22908-0735, USA Our lab and others have looked at the RVLM’s role in reflex responses to different homeostatic challenges such as hypotension, hypoxia, and hypoglycemia. The general belief is that the RVLM utilizes glutamate as the primary transmitter in response to these homeostatic challenges; however, this has never been proven in-vivo. Guyenet’s laboratory utilized a combination of optogenetics, immunohistochemistry, and multi-cell recordings in gene knockout mice in an attempt to confirm that these responses are glutamate-mediated. In particular, they were looking at the role of a glutamate transporter VGLUT2. They used DβHCre/0 mice which mark noradrenergic and adrenergic neurons with Cre-recombinase. In addition to this they paired the DβHCre/0 with rats that knock out the VGLUT-2 gene, called cKO mice. By utilizing DβHCre/0 and cKO mice using optogenetics, the team was able to determine the role of glutamate and VGLUT-2 in these responses. They found that VGLUT-2 deletion has no effect on the number or morphology of C1 neurons in RVLM, but completely eliminated several homeostatic responses. The acute respiratory and parasympathetic activation produced via optogenetic stimulation was abolished following removal of VGLUT-2. It would be interesting to do this same study, but incorporate the non-C1 neurons via some other technique. Most importantly though, this once again plays into Guyenet’s belief that C1 neurons function to maintain homeostasis following different physiologic challenges, that C1 neurons are the body’s EMTs and glutamate is the main means by which the RVLM affects the periphery. At some point we could look at adding optogenetics into our experiments, perhaps even with MEMRI. -M.T.L.