(Verbatim from the application): The long-term goal of my research is to establish the brainstem circuits through which trigeminal neurons modulate cardiovascular and respiratory activity in mammals. The cardiorespiratory depression (the diving response) seen after stimulation of he upper respiratory tract (URT) has served as my model.
The aims for this proposal are directed towards elucidating the control of blood pressure, specifically in regard to both nasal and muscle stimulation. We shall focus our attention on the interplay between the caudal pressor area (CPA) and its interaction with the premotor sympathetic bulbospinal neurons of the rostroventrolateral medulla RVLM). Since the CPA is basically undefined in the rat, two of our aims are directed to locating it and demonstrating its connections, especially with the RVLM. Two other aims will define its role in blood pressure regulation in general as well as to nasal nd muscle stimulation. A fifth aim will define the primary afferent termination of sensory fibers innervating the triceps sure muscle in the rat. We propose specifically to 1) localize the CPA in the caudal medulla; 2) define the input/output of the CPA; 3) define the central termination of sensory fibers to the triceps sure muscle; 4) determine the role of the CPA during the diving esponse and muscle stimulation; and, 5) characterize the responses of individual neurons in the CPA to hypertensive, hypotensive, oxious, and nasal and muscle stimuli. The CPA has been defined in variable positions within the caudal medulla depending on the species in question.
Aim I specifically will identify its location in the rat. Blood pressure will be recorded after stimulating the caudal medulla; such a procedure should localize the pressor areas there. Two complimentary neuroanatomical methodologies will determine the output/input of the PA, especially to the RVLM, as outlined in Aim II The orthogradely transported tracer biotinylated dextrin amine and the retrogradely transported tracer fluorogold will elucidate projections from/to the CPA. There is some controversy regarding the input o the dorsal horn of primary afferent fibers from muscle.
Aim III will use transganglionic transport of HRP to investigate this roblem and correlate this data to that seen in Aim II.
In Aim I V, the CPA will be tested to determine its role in controlling blood pressure to both nasal and muscle stimulation. Chemical lesions using ibotenic acid will be made in the CPA and changes in cardiovascular behavior to such stimulation determined. Finally, neurons in the CPA will be monitored electrophysiologically in Aim V and their responses recorded to hypertensive, hypotensive, noxious, and nasal and muscle stimuli. This study will provide the most complete study of the CPA, about which little is known. Stimulation of the URT or large muscles in man causes an increase in sympathetic discharge and hypertension. Understanding the brainstem mechanisms governing he vascular constriction after either of these somatic stimuli may provide a neurological explanation for this. Such knowledge may lead to an understanding of essential hypertension.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL064772-04
Application #
6688249
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Program Officer
Velletri, Paul A
Project Start
2001-01-01
Project End
2006-12-31
Budget Start
2004-01-01
Budget End
2006-12-31
Support Year
4
Fiscal Year
2004
Total Cost
$259,000
Indirect Cost
Name
Saint Louis University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
050220722
City
Saint Louis
State
MO
Country
United States
Zip Code
63103
Panneton, W Michael; Gan, Qi; Ariel, Michael (2015) Injections of Algesic Solutions into Muscle Activate the Lateral Reticular Formation: A Nociceptive Relay of the Spinoreticulothalamic Tract. PLoS One 10:e0130939
Panneton, W Michael (2013) The mammalian diving response: an enigmatic reflex to preserve life? Physiology (Bethesda) 28:284-97
Panneton, W Michael; Gan, Qi; Sun, D Wei (2012) Persistence of the nasotrigeminal reflex after pontomedullary transection. Respir Physiol Neurobiol 180:230-6
Panneton, W Michael; Gan, Qi; Livergood, Robert S (2011) A trigeminoreticular pathway: implications in pain. PLoS One 6:e24499
Panneton, W Michael; Hsu, Hugo; Gan, Qi (2010) Distinct central representations for sensory fibers innervating either the conjunctiva or cornea of the rat. Exp Eye Res 90:388-96
Panneton, W Michael; Gan, Qi; Juric, Rajko (2010) The rat: a laboratory model for studies of the diving response. J Appl Physiol 108:811-20
Panneton, W Michael; Gan, Qi; Dahms, Thomas E (2010) Cardiorespiratory and neural consequences of rats brought past their aerobic dive limit. J Appl Physiol 109:1256-69
Burke, William J; Kumar, Vijaya B; Pandey, Neeraj et al. (2008) Aggregation of alpha-synuclein by DOPAL, the monoamine oxidase metabolite of dopamine. Acta Neuropathol 115:193-203
Panneton, W Michael; Sun, Wei; Gan, Qi (2008) Pressor responses to nasal stimulation are unaltered after disrupting the CPA. Auton Neurosci 144:13-21
Pan, Yi; Zhang, Haibo; VanDeripe, Donald R et al. (2007) Heliox and oxygen reduce infarct volume in a rat model of focal ischemia. Exp Neurol 205:587-90

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