Glenn M. Toney, Ph.D.
Neurons in the PVN receive many different types of sensory input and can produce a variety of effects mediated through the sympathetic nervous system. Prominent among PVN neurons comprising sympathetic efferent pathways are those that form monosynaptic connections with the rostral ventrolateral medulla (rVLM) and the nucleus tractus solitarius (NTS) in the hindbrain and the intermediolateral cell column (IML) in the spinal cord. Connectivity and functional studies provide evidence that the PVN is a critically important site for central control of cardiovascular and body fluid regulatory functions.
Our recent work, and that of others, indicates that autonomic PVN neurons are recruited following specific changes in extracellular fluid volume and osmolarity. At present, however, we do not know if volume and osmotic disturbances are mediated by separate (i.e., spatially distinct) PVN pathways or if common descending efferents are activated in response to both sensory inputs. How individual neurons in specific PVN pathways respond to volume and/or osmotic challenges is beginning to be revealed through in vivo electrophysiological approaches. The underlying neurotransmitter mechanisms and intracellular signaling cascades that mediate these discharge responses are not fully understood, but L-glutamate and the neuropeptide angiotensin II are likely candidates. We are seeking to expand understanding of PVN control of specific efferent pathways using in vivo and brain slice electrophysiological techniques, optogenetics, viral transduction, neuroanatomical methods as well as integrative whole animal approaches .
Major goals for my lab are to provide new knowledge regarding the basic function of specific groups of autonomic neurons and to determine how these groups of neurons are involved in cardiovascular disease. We are currently interested in determining how the PVN contributes to autonomic disturbances that accompany angiotensin II- and sodium-sensitive models of hypertension as well as congestive heart failure. Studies currently underway are designed to provide new insights into the pathologic changes in neurotransmission that occur in these cardiovascular diseases. These efforts represent an important step toward the development of centrally acting drugs that effectively reduce sympathetic activity in patients with hypertension or heart failure without producing episodes of severe hypotension characteristic of current centrally acting sympatholytic treatments
Megan Bardgett, Ph.D.
Holbein WW and Toney GM. Sympathetic Network Drive During Water Deprivation Does Not Increase Respiratory or Cardiac Rhythmic Sympathetic Nerve Activity. J Appl Physiol. 114(12):1689-96. 2013. PMCID: PMC3680821.
Sharpe AL, Andrade MA, Herrera-Rosales M, Britton SL, Koch LG, Toney GM. Rats Selectively Bred for Differences in Aerobic Capacity Have Similar Hypertensive Responses to Chronic Intermittent Hypoxia. Am J Physiol Heart Circ Physiol. 305(3):H403-9. 2013. PMID: 23709603
Toney GM, Vallon V, Stockand JD. Intrinsic control of sodium excretion in the distal nephron by inhibitory purinergic regulation of the epithelial Na(+) channel. Curr Opin Nephrol Hypertens. 2012 Jan;21(1):52-60. Review. PMID: 22143248 [PubMed - indexed for MEDLINE]