(Verbatim from the application): Glutamate is the major neurotransmitter in primary afferents to the nucleus of the solitary tract (NTS), including baroreceptive afferents. The proposed studies will examine the receptor substrates for glutamatergic excitation of neurons involved in central autonomic control at sensory sites in the NTS. Since the ionotropic receptors have been most strongly implicated in regulating autonomic responses in the NTS, we will first characterize the cellular distribution of each of these receptors in the medial NTS, the primary termination site for baroreceptor afferents (Aim 1). The anatomical location of each receptor is fundamentally related to its functional role (e.g. presynaptic receptors regulate release from axon terminals, while postsynaptic receptors mediate excitatory responses). The proposed studies will use immunocytochemical localization of receptor proteins from three types of ionotropic glutamate receptors (NMDA, AMPA and kainate). Electron microscopy will resolve the subcellular location of these receptive sites. Baroreceptor afferents contained in the aortic depressor nerve (ADN) are involved in cardiovascular autonomic regulation, so anterograde labeling of these afferents will be used to identify autonomic neurons in the NTS (Aim 1.b). The glutamate receptor distribution on these afferents and their targets will be examined. In other studies, second-order baroreceptive NTS neurons, which show monosynaptic responses to stimulation of the solitary tract in the slice preparation and are apposed by anterogradely labeled boutons from the ADN, will be intracellularly filled and the glutamate receptor will be immunocytochemically localized on the same cell (Aim 1 .c). To assess their role in central autonomic plasticity, glutamate receptor subunits that are located in NTS autonomic neurons will be quantitatively examined after chronic hypertension for signs of receptor up- or down-regulation, or internalization, using both optical densitometry and immunocytochemical receptor labeling with electron microscopy (Aim 2). The goal of this project is to understand the cellular substrates for regulation of NTS autonomic neurons both spatially (over the surface of the cell) and temporally (in different physiological states), and to relate this structural information to the physiological properties of these neurons. These studies will establish a structural basis for acute and chronic plasticity in NTS. The long-term goal of this project is to understand the cellular basis for receptor modulation of central autonomic neuronal activity.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL056301-05
Application #
6498938
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Program Officer
Velletri, Paul A
Project Start
1997-08-28
Project End
2004-01-31
Budget Start
2002-02-01
Budget End
2003-01-31
Support Year
5
Fiscal Year
2002
Total Cost
$226,500
Indirect Cost
Name
Oregon Health and Science University
Department
Type
Schools of Medicine
DUNS #
009584210
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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