Central Nervous System Regulation of Cardiovascular Function

John Cabot
John B. Cabot
Professor
PhD, University of Virginia

Michael Ligorio, Postdoctoral Fellow
Wendy Akmentin - Research Technician
The central nervous system plays a fundamental role in the regulation of peripheral arterial blood pressure and cardiac function. While this generalization has long been known it has only been over the last decade that significant progress has been achieved on the identification of pathways, neurotransmitters and receptors involved. In spite of the progress, a lack of neuroanatomical and neurochemical data still remains a significant limiting factor for further defining where and what specific changes in brain lead to: (1) expression of certain forms of primary hypertension, and (2) cardiovascular hyperexcitability (autonomic dysreflexia) following severe spinal cord injury.

The experimental efforts in this laboratory concentrate on neuroanatomical studies of spinal cord. This focus is premised on the fact that the autonomic outflow (sympathetic preganglionic neurons) from thoracic spinal cord is the central nervous system "final common pathway" for the control of blood pressure and cardiac function. Any normal and abnormal behavior of "cardiovascular circuits" within brain will necessarily be reflected in changes in the spinal sympathetic preganglionic outflow. This means that we will ultimately have to know in detail: (1) the normal physiology of sympathetic preganglionic neurons, (2) the identity of the neural pathways synapsing on these neurons, (3) the identity of the neurotransmitters released by "cardiovascular" pathway inputs to these cells, and (4) the identification and localization of ligand-gated receptors in the membranes of sympathetic preganglionic neurons.

The research in the laboratory explores many of these issues. Neuroanatomy, as practiced by us, is broadly defined and encompasses: (1) light and electron microscopy, (2) immunohistochemical localization of neurotransmitter and receptor antigens, and (3) pathway identification using anterograde, retrograde and transneuronal tracers. Specific goals of current research projects include: (1) identification, characterization, and localization of glutamatergic, GABAergic and glycinergic amino acid neurotransmitter inputs to sympathetic preganglionic neurons, (2) investigations of the changes in these amino acid neurotransmitter inputs and their associated receptors following severe spinal cord injury, and (3) characterizationof the intracellular transport and transneuronal translocation of the binding fragment of tetanus toxin.

Relevant Publications:

Cabot, J.B., Alessi, V., Carroll, J. and Ligorio, M. (1994) Spinal cord lamina V and lamina VII interneuronal projections to sympathetic preganglionic neurons. J.Comp.Neurol. 347:515-530.

Cabot, J.B., Bushnell, A., Alessi, V. and Mendell, N.R. (1995) Postsynaptic gephyrin immunoreactivity exhibits a nearly one-to-one correspondence with GABA-like immunogold labeled synaptic inputs to sympathetic preganglionic neurons. J.Comp.Neurol. 356:418-432.

Cabot, J.B. (in press) Some principles of the spinal organization of the sympathetic preganglionic outflow. Prog. Brain Res.