User:Bartond/Area Postrema Project Proposal

Area Postrema Project Proposal
The initial research for the area postrema project was divided into four major categories for each student in the group to explore. After assessing these first findings we will divide up the remaining research, adjusting where necessary, in order to equalize each group member’s work load. The four major categories were “Anatomy and connectivity,” “Function,” “Pathology/disease,” and “History of research/Current research.” The categories were explored by Jess, Danielle, Nick, and Lauren, respectively.

Anatomy and Connectivity
The area postrema is located within the medulla oblongata of the brain stem. More specifically, it is a protuberance found on each side of the fourth ventricle, one of four fluid-filled cavities within the human brain. This location situates this circumventricular organ outside of the blood-brain barrier. The area postrema is connected via nerve fibers to the solitary nucleus, spinal cord and other areas of the medulla.

Function
The area postrema is a critical homeostatic integration center for humoral and neural signals. Recent studies have implicated its role as a chemoreceptor trigger zone for vomiting in response to emetic drugs. Its position outside of the blood-brain barrier makes this particular region of the medulla a key player in the control of autonomic functions, including the cardiovascular system and systems controlling feeding and metabolism. Area postrema is now being considered as the initial site for integration for various physiological signals in the blood as they enter the central nervous system.

Pathology/Disease
Since the area postrema acts as an entry point to the brain for information from the sensory neurons of the stomach, intestines, liver, kidneys, heart, and other internal organs, a variety of the physiological reflexes rely on the area postrema to transfer information. The area postrema also acts to directly monitor the chemical status of the organism. first indent Lesions of the area postrema are sometimes referred to as ‘central vagotomy’ because of their ability to eliminate the brain’s ability to monitor the physiological status through its vagus nerve. These lesions also serve to prevent the detection of poisons and consequently prevent the body’s natural defenses from kicking in. For example, studies in rats and rabbits indicate that angiotension II- dependent hypertansion is abolished by lesioning of the area postrema. In another experiment with rats, the area postrema lesions prevented the detection of Lithium Chloride, which can become toxic at high concentrations. Since the rats could not detect the chemical, they were not able to employ a psychological procedure known as taste aversion conditioning, causing the rat to continuously ingest the toxic chemical when added to its food.

History of Research/Current Research
Several scientists played important roles in the study of vomiting, beginning in the 1950s with the research of Herbert L. Borison and his colleagues. Borison received his doctorate in 1948 from Colombia University where he had become an authority on brainstem and neurophysiology. Perhaps in some ways prompted by societal attention at the time on radiation sickness, in which many patients who vomited after radiation exposure died, studies on vomiting began in the 1950s at the University of Utah College of Medicine where Borison had a strong presence as both a professor and a researcher. Borison’s collaboration with S.C. Wang, a doctor from Columbia University, led to their determination of the existence of a vomiting trigger zone in the brain stem in 1953, which they called then a chemoreceptor trigger zone (CTZ) for emesis and which was anatomically identified as the area postrema of the medulla oblongata. The function of this circumventricular organ had been previously unknown and following the work of Borison and Wang is has been confirmed by many laboratories. They also created what is known as the Borison-Wang model of emesis which includes a diagram showing the concept of the vestibular emetic pathway connecting through the area postrema as the obligatory route to the emetic center. However, more recent research has shown this model to be incorrect. Other scientists who have been noted as pioneers in the field of research concerning the area postrema and the mechanism of vomiting in general are Kenneth R. Brizzee, Larry McCarthy, A.D. Miller and V. J Wilson. Research has continued today on the mechanism of vomiting and on the role of the area postrema in this mechanism. Much of the experimentation has been performed on such animals as cats, dogs and monkeys.