Convergent central pathways for sympatho-inhibition

Medical College Of Wisconsin, Milwaukee WI

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Abstract

DESCRIPTION (provided by applicant): 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.