ANATOMICAL STUDIES OF BRAINSTEM CARDIOVASCULAR SYSTEMS

Project: Research project

Description

DESCRIPTION: A subregion of the gigantocellular reticular formation, the Gigantocellular Depressor Area (GiDA), contains both vasodepressor sites and reticulospinal neurons. The GiDA receives catecholaminergic terminals and contains alpha2A-adrenergic receptors (ARs) that may play a role in the anti-hypertensive actions of alpha2A -adrenergic drugs. The working hypothesis is that catecholaminergic afferents modulate GiDA vasodepressor neurons via alpha2A-ARs and this pathway may be an endogenous substrate for anti-hypertensive therapies. Four sets of experiments in rats are proposed: Experiment I will determine if reticulospinal neurons in the GiDA are also blood pressure sensitive. This finding would support a direct role for the reticulospinal neurons in the cardiovascular functions of this brain area. Experiment 2 will determine the anatomical substrates for GiDA vasodepressor function. Tract tracing studies will identify potential sources of input, including catecholaminergic afferents, as well as efferent projections to cholinergic sympathetic preganglionic neurons in the spinal cord. These studies will show how the GiDA is integrated with other autonomic areas. Experiment 3 will determine if: (a) alpha2A-ARs in the GiDA are involved in cardiovascular responses evoked by microinjections of adrenergic agonists into this area; and (b) catecholaminergic terminals synapse on reticulospinal neurons that are thought to mediate the vasodepressor responses of the GiDA. Together these studies will clarify the role of endogenous catecholamines and exogenous adrenergic agonists in the modulation of cardiovascular neurons in the GiDA. Experiment 4 will determine if alpha2A-AR immunoreactivity is post-synaptic to catecholaminergic terminals and located within reticulospinal neurons in GiDA. These studies will define the anatomical substrate for 2A-AR mediated actions in GiDA, including the anti-hypertensive effects of adrenergic drugs. The overall goals of this proposal are to establish the function and anatomy of this unique medullary sympathoinhibitory region, its integration into cardiovascular networks, and to examine alternative mechanisms of anti-hypertensive drug therapy.
StatusFinished
Effective start/end date8/28/974/30/09

Funding

  • National Institutes of Health: $226,500.00
  • National Institutes of Health: $191,389.00
  • National Institutes of Health: $182,012.00
  • National Institutes of Health
  • National Institutes of Health: $250,559.00
  • National Institutes of Health: $264,250.00
  • National Institutes of Health: $258,041.00
  • National Institutes of Health: $264,250.00
  • National Institutes of Health: $226,500.00
  • National Institutes of Health: $226,500.00

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Cardiovascular System
Brain Stem
Neurons
Glutamate Receptors
Adrenergic Receptors
Hypertension
Antihypertensive Agents
AMPA Receptors
Baroreflex
Solitary Nucleus
Pressoreceptors
Adrenergic Agonists
Electron Microscopy
Dendritic Spines
Adrenergic Agents
Neuronal Plasticity
Presynaptic Receptors
Ionotropic Glutamate Receptors
Blood Pressure
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid

ASJC

  • Medicine(all)