Contact

Department

Cellular and Integrative Physiology

Glenn M. Toney, Ph.D.

Ashbel Smith Professor

Education

B.S., Weber State College, 1988
Ph.D., University of Louisville, 1992

Research

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

Lab Members

 

 Mary Ann Andrade
Research Associate – Senior
Postdoctoral Fellow
Tamara Truong
Research Technician – Intermediate
Postdoctoral Fellow
Postdoctoral Fellow

Publications

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]

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.

Knight WD, Little JT, Carreno FR, Toney GM, Mifflin SW, Cunningham JT. Am J Physiol Regul Integr Comp Physiol. 2011 Jul;301(1):R131-9. Epub 2011 May 4. Chronic intermittent hypoxia increases blood pressure and expression of FosB/DeltaFosB in central autonomic regions.

Knight WD, Little JT, Carreno FR, Toney GM, Mifflin SW, Cunningham JT. Chronic intermittent hypoxia increases blood pressure and expression of FosB/DeltaFosB in central autonomic regions. Am J Physiol Regul Integr Comp Physiol. 2011 Jul;301(1):R131-9. Epub 2011 May 4. PMID: 21543638 [PubMed – indexed for MEDLINE]

King TS, Toney GM, Tian PY, Javors MA. Dehydration increases sodium-dependent glutamate uptake by hypothalamic paraventricular nucleus synaptosomes. Neuro Endocrinol Lett. 2011;32(6):763-8. PMID: 22286787 [PubMed – indexed for MEDLINE]

Toney GM, Cunningham JT, Mifflin SW. (2010) Early neural adaptations to intermittent hypoxia: Triggers for the pathophysiology of sleep apnea. In A. Ally, TJ Maher, JM Wyss (Eds.), (pp. 75-96). Recent Advances in Cardiovascular Research: From Sleep to ExerciseKerala, India: Transworld Research Network.

Toney GM, Stocker SD. Hyperosmotic activation of CNS sympathetic drive: implications for cardiovascular disease. J Physiol. 2010 Sep 15;588(Pt 18):3375-84.

Toney GM. Regulation of neuronal cell volume: from activation to inhibition to degeneration. J Physiol. 2010 Sep 15;588(Pt 18):3347-8.

France CP, Li JX, Owens WA, Koek W, Toney GM, Daws LC. Reduced effectiveness of escitalopram in the forced swimming test is associated with increased serotonin clearance rate in food-restricted rats.Int J Neuropsychopharmacol. 2009 Jul;12(6):731-6.

Cardoso LM, Colombari DS, Menani JV, Toney GM, Chianca-Jr DA, Colombari E. Cardiovascular Responses to Hydrogen Peroxide into the Nucleus Tractus Solitarius. Am J Physiol Regul Integr Comp Physiol. 2009 Jun 10.

Shi P, Martinez MA, Calderon AS, Chen Q, Cunningham JT, Toney GMIntra-Carotid hyperosmotic stimulation increases Fos staining in OVLT neurones that project to the hypothalamic PVN. J Physiol. 2008 Aug 28.

 

Baganz NL, Horton RE, Calderon AS, Owens WA, Munn JL, Watts LT, Koldzic-Zivanovic N, Jeske NA, Koek W, Toney GM, Daws LC. Organic cation transporter 3: Keeping the brake on extracellular serotonin in serotonin-transporter-deficient mice. Proc Natl Acad Sci U S A. 2008 Dec 2;105(48):18976-81.

Shi P, Stocker SD, Toney GMOrganum vasculosum laminae terminalis contributes to increased sympathetic nerve activity induced by central hyperosmolality. Am J Physiol Regul Integr Comp Physiol. 2007 Dec;293(6):R2279-89.

Stocker SD, Simmons RJ, Stornetta RL, Toney GM and Guyenet PG. Water Deprivation Activates a Glutamatergic Projection from the Hypothalamic Paraventricular Nucleus to the Rostral Ventrolateral Medulla. J Comp Neurol 494(4): 673-685, 2006.

Li H, Gao Y, Freire CD, Raizada MK, Toney GM and Sumners C. Macrophage migration inhibitory factor in the PVN attenuates the central pressor and dipsogenic actions of angiotensin II. FASEB J 20(10): 1746-56, 2006.

 

Stocker SD, Hunwick KJ and Toney GMHypothalamic paraventricular nucleus differentially supports lumbar and renal sympathetic outflow in water-deprived rats. J Physiol (London) 563: 249-263, 2005

Toney GM, Chen QH, Cato MJ and Stocker SD. Central osmotic regulation of sympathetic nerve activity. Acta Physiol Scand 177(1): 43-55, 2003.