Target-Dependent Feedback Regulation of Neural Activity

University Of North Carolina At Chapel Hill, Chapel Hill NC

Investigators

Abstract

The brain innervates all the organs in the body, and controls and coordinates their activities. However, the brain can only do this effectively if it has accurate information about the status of its targets. The Goy laboratory is interested in learning how target organs communicate with neural circuits. They have begun to investigate feedback regulation of a simple neural circuit (the crustacean cardiac ganglion), which controls the contractions of the heart musculature. Their preliminary data show that this system uses a novel form of muscle-to-nerve feedback, based on a paracrine signaling factor known as nitric oxide (NO). The feedback scheme is simple. Nitric oxide synthase (NOS), the enzyme that makes NO, is present in crustacean heart muscle fibers at very high levels. Cardiac NOS is stimulated by calcium. Heart muscle contractions are also triggered by calcium. Thus, with each heartbeat, the muscle is thought to produce a burst of NO whose amplitude and timing encode information about the performance of the heart. The NO can diffuse quickly to the ganglion, which lies within the chamber of the heart (completely surrounded by the muscle). The effect of NO is to strongly suppress the output of the ganglion. Taken in a physiological context, this actually makes very good sense: if the heart is beating too fast or too hard it will make disproportionate amounts of NO, which will inhibit the ganglion, and -- because the ganglion provides the stimuli that drive the muscle -- will ultimately bring muscle contractions back into a more satisfactory range. The experiments outlined in Dr. Goy's proposal are designed to test these ideas, and to learn more about the mechanisms that underlie this unusual feedback pathway. Dr. Goy is a mentor in the UNC Research Apprenticeship Program, which provides academically gifted Minority high school students with a 3-month summer research experience. He is also a UNC undergraduate research mentor. Over the last 10 years he has provided 11 UNC biology and chemistry students with intensive research training in his laboratory. A portion of the supply budget will be used to support the efforts of a high school or college student each summer for the duration of the award.