The central nervous system coordinates appropriate behavioral and physiological events in response to imposed environmental challenges but many mechanisms remain to be determined. The present study will focus on a single component which is common to a number of behaviors and conditions to determine whether convergent central pathways exist. Sympatho-inhibition is fundamental to both the recovery phase of a defense response and also to the response to severe hemorrhage. The present proposal is designed to characterize central pathways mediating sympatho-inhibition during these conditions and determine if the sympatho-inhibition is mediated by convergence to a common central pathway. Background and preliminary data suggests that under both conditions sympatho-inhibition is mediated through a final common pathway via 5-HTIA receptors in the sympatho-excitatory region of the rostroventrolateral medulla (RVLM). This would provide a novel serotonergic pathway generating sympatho-inhibition which is distinct from that mediating reflex sympatho-inhibition via GABA receptors on sympatho-excitatory neurons. The proposed studies will extend a finding that a sympatho-inhibition elicited from the ventrolateral periaqueductal gray matter is mediated through activation of 5-HTIA receptors in the RVLM. Sympathetic nerve and central unit recordings combined with microinjection techniques will be utilized to investigate the pathway mediating sympatho-inhibition from the periaqueductal gray via RVLM 5-HTIA receptors, and determine its involvement in the recovery phase of a defense response. Studies will also examine a putative role for activation of 5-HTIA receptors in the RVLM during extreme hemorrhage. The results of these studies will provide insight into the extent of convergence of central pathways mediating sympatho-inhibition during the recovery phase of a defense response and during extreme hemorrhage. The long-term aim of this proposal is to characterize a pathway which may mediate a specific neural response essential to multiple conditions. These novel data will be of potential significance to an array of pathologies and behaviors including emotional behaviors, analgesia, shock, sexual function and fainting.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS043189-02
Application #
6622920
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Mitler, Merrill
Project Start
2002-03-15
Project End
2006-02-28
Budget Start
2003-03-01
Budget End
2004-02-29
Support Year
2
Fiscal Year
2003
Total Cost
$126,000
Indirect Cost
Name
Medical College of Wisconsin
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
937639060
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
Dean, C (2005) Sympathoinhibition from ventrolateral periaqueductal gray mediated by the caudal midline medulla. Am J Physiol Regul Integr Comp Physiol 289:R1477-81
Seagard, Jeanne L; Hopp, Francis A; Hillard, Cecilia J et al. (2005) Effects of endocannabinoids on discharge of baroreceptive NTS neurons. Neurosci Lett 381:334-9
Dean, Caron (2004) Hemorrhagic sympathoinhibition mediated through the periaqueductal gray in the rat. Neurosci Lett 354:79-83
Dean, C; Woyach, V L (2004) Serotonergic neurons of the caudal raphe nuclei activated in response to hemorrhage in the rat. Brain Res 1025:159-68