The ventral medulla oblongata regulates sympathetic efferent activity to the cardiovascular system. Neurons containing substance P (SP) and thyrotropin releasing hormone (TRH) project from the ventral medulla to the spinal cord intermediolateral cell column (IML) (the site of origin of preganglionic sympathetic neurons). Pharmacologic experiments suggest that SP mediates sympathoexcitatory responses elicited from the ventral medulla. The proposed experiments are intended (1) to further elucidate the role of SP and TRH in the ventral medullary regulation of cardiovascular function by studying the cellular location of TRH receptors and sympathetic cardiovascular effects of IML TRH receptor activation, by assessing in vivo the effects of ventral medullary activation on an index of SP and TRH turnover, and by determining the effects of SP and TRH analogs on regional spinal cord and peripheral blood flow; and (2) to provide more complete information on the chemical neuroanatomy of the ventral medulla by studying the origin, and cellular location of terminals and receptors of the tonically active GABAergic innervation of ventral medullary SP and TRH neurons, and to evaluate SP and TRH coexistence in nonserotonergic neurons in the ventral medulla and terminals in the IML. We will use neuroanatomical and neurochemical techniques (neuronal tract tracing, immunocytochemistry, receptor autoradiography, peptide turnover, radioimmunoassay), and in vivo neuropharmacological techniques (CNS injections and monitering of heart rate, blood pressure, and regional blood flow). These studies will provide information on the chemical neuroanatomy and functional role of efferent (SP, TRH) and afferent (GABA) neuronal systems of the ventral medulla. This information is vital to the understanding of CNS control of the cardiovascular system and may enable the design of new therapeutic approaches and drugs to treat and/or prevent cardiovascular diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS024876-01
Application #
3409848
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1986-08-01
Project End
1989-07-31
Budget Start
1986-08-01
Budget End
1987-07-31
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Henry M. Jackson Fdn for the Adv Mil/Med
Department
Type
DUNS #
City
Rockville
State
MD
Country
United States
Zip Code
20852
Helke, C J; Capuano, S; Tran, N et al. (1997) Immunocytochemical studies of the 5-HT(1A) receptor in ventral medullaryneurons that project to the intermediolateral cell column and contain serotonin or tyrosine hydroxylase immunoreactivity. J Comp Neurol 379:261-70
Routh, V H; Helke, C J (1997) A novel technique for producing antibody-coated microprobes using a thiol-terminal silane and a heterobifunctional crosslinker. J Neurosci Methods 71:163-8
Yang, L; Thomas, N D; Helke, C J (1996) Characterization of substance P release from the intermediate area of rat thoracic spinal cord. Synapse 23:265-73
Nevin, K; Zhuo, H; Helke, C J (1994) Neurokinin A coexists with substance P and serotonin in ventral medullary spinally projecting neurons of the rat. Peptides 15:1003-11
Yang, L; Jacocks 3rd, H M; Helke, C J (1994) Release of [3H]5-hydroxytryptamine from the intermediate area of rat thoracic spinal cord is modulated by presynaptic autoreceptors. Synapse 18:198-204
Helke, C J; McDonald, C H; Phillips, E T (1993) Hypotensive effects of 5-HT1A receptor activation: ventral medullary sites and mechanisms of action in the rat. J Auton Nerv Syst 42:177-88
Thor, K B; Nickolaus, S; Helke, C J (1993) Autoradiographic localization of 5-hydroxytryptamine1A, 5-hydroxytryptamine1B and 5-hydroxytryptamine1C/2 binding sites in the rat spinal cord. Neuroscience 55:235-52
Zhuo, H; Helke, C J (1993) Neurokinin B peptide-2 neurons project from the hypothalamus to the thoracolumbar spinal cord of the rat. Neuroscience 52:1019-28
Thor, K B; Blitz-Siebert, A; Helke, C J (1992) Autoradiographic localization of 5HT1 binding sites in autonomic areas of the rat dorsomedial medulla oblongata. Synapse 10:217-27
Thor, K B; Blitz-Siebert, A; Helke, C J (1992) Autoradiographic localization of 5HT1 binding sites in the medulla oblongata of the rat. Synapse 10:185-205

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