Glutamate receptors, particularly AMPA receptors, in the nucleus of the solitary tract (NTS) are the 3rimary mechanism for synaptic transmission between primary afferents and second-order neurons. Thus, an understanding of glutamate receptors in NTS is vital to understanding autonomic reflexes. In our previous studies of AMPA receptors we made a surprising discovery: the number of GluR1 receptor subunits significantly increases in NTS following the development of hypertension. This finding is particularly intriguing since GluR1 is found in dendritic spines, which are widely associated with synaptic plasticity in the brain. Our hypothesis is that structural remodeling in NTS neurons during hypertension leads to functional changes in individual NTS neurons that in turn contribute to alterations in the baroreceptor reflex pathway, such as central baroreflex resetting. These structural changes are found in regions of NTS that contain baroreceptive afferents and second-order neurons, but we do not know which NTS neurons contain GluRI. In the present experiments we will use a multidisciplinary approach to: (1) determine which population(s) of NTS neurons contain GluR1; (2) examine the structural and functional changes in NTS neurons following the development of hypertension; and (3) address the functional relationship between this structural neuronal change and blood pressure. The combined efforts of the Aicher and Andresen laboratories bring together expertise in anatomical and physiological techniques. This collaborative project provides a unique opportunity to directly address structural and physiological questions regarding NTS neuronal function in both the normal and hypertensive states. ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL056301-10
Application #
7224276
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Thrasher, Terry N
Project Start
1997-08-28
Project End
2009-04-30
Budget Start
2007-05-01
Budget End
2009-04-30
Support Year
10
Fiscal Year
2007
Total Cost
$250,559
Indirect Cost
Name
Oregon Health and Science University
Department
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Hermes, Sam M; Andresen, Michael C; Aicher, Sue A (2016) Localization of TRPV1 and P2X3 in unmyelinated and myelinated vagal afferents in the rat. J Chem Neuroanat 72:1-7
Hermes, Sam M; Colbert, James F; Aicher, Sue A (2014) Differential content of vesicular glutamate transporters in subsets of vagal afferents projecting to the nucleus tractus solitarii in the rat. J Comp Neurol 522:642-53
Cassaglia, Priscila A; Hermes, Sam M; Aicher, Sue A et al. (2011) Insulin acts in the arcuate nucleus to increase lumbar sympathetic nerve activity and baroreflex function in rats. J Physiol 589:1643-62
Hegarty, Deborah M; Tonsfeldt, Karen; Hermes, Sam M et al. (2010) Differential localization of vesicular glutamate transporters and peptides in corneal afferents to trigeminal nucleus caudalis. J Comp Neurol 518:3557-69
Parrish, Diana C; Alston, Eric N; Rohrer, Hermann et al. (2009) Absence of gp130 in dopamine beta-hydroxylase-expressing neurons leads to autonomic imbalance and increased reperfusion arrhythmias. Am J Physiol Heart Circ Physiol 297:H960-7
Morgan, Michael M; Whittier, Kelsey L; Hegarty, Deborah M et al. (2008) Periaqueductal gray neurons project to spinally projecting GABAergic neurons in the rostral ventromedial medulla. Pain 140:376-86
Hermes, Sam M; Mitchell, Jennifer L; Silverman, Marc B et al. (2008) Sustained hypertension increases the density of AMPA receptor subunit, GluR1, in baroreceptive regions of the nucleus tractus solitarii of the rat. Brain Res 1187:125-36
Thomson, Lisa M; Terman, Gregory W; Zeng, Jinsong et al. (2008) Decreased substance P and NK1 receptor immunoreactivity and function in the spinal cord dorsal horn of morphine-treated neonatal rats. J Pain 9:11-9
Hegarty, Deborah M; Mitchell, Jennifer L; Swanson, Kristin C et al. (2007) Kainate receptors are primarily postsynaptic to SP-containing axon terminals in the trigeminal dorsal horn. Brain Res 1184:149-59
Bailey, T W; Hermes, S M; Whittier, K L et al. (2007) A-type potassium channels differentially tune afferent pathways from rat solitary tract nucleus to caudal ventrolateral medulla or paraventricular hypothalamus. J Physiol 582:613-28

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