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. Studies that have demonstrated these connections combined with 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, 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 also unknown as are the underlying neurotransmitter mechanisms and intracellular mediators of such changes. We are seeking to provide this information through the combined use of electrophysiological techniques, neuroanatomical methods and integrative cardiovascular approaches at the level of the whole animal. We are also using cellular approaches to study intracellular signalling in these important groups of autonomic regulatory neurons.
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.
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]
Cardoso LM, Colombari E, Toney GM. Endogenous hydrogen peroxide in the hypothalamic paraventricular nucleus regulates sympathetic nerve activity responses to L-glutamate. J Appl Physiol 113: 1423–1431, 2012.
Daws LC, Toney GM. In: Michael AC, Borland LM, editors. Electrochemical Methods for Neuroscience. Boca Raton (FL): CRC High-Speed Chronoamperometry to Study Kinetics and Mechanisms for Serotonin Clearance In Vivo.