IBN98-08616 VILLALOBOS Choline is an immediate precursor to acetylcholine, the neurotransmitter for the central neuronal pathways involved in sleep-wake cycling and learning or memorization. The amount of choline is rate-limiting in the synthesis of acetylcholine. Therefore, maintaining appropriate levels of choline in the fluid that bathes the neurons in the brain is critical to both their individual and integrative function. Most of this extracellular fluid is produced by the choroid plexus, a very small non-neuronal organ, weighing about 2 grams in the average adult human. It is located in the ventricles, or cavities, of the brain. The choroid plexus also plays an important role in regulating the levels of choline, as well as other inorganic and organic ions, in the extracellular fluid by transporting choline from the brain into the blood. More precisely, specialized cells of the choroid plexus are responsible for the transport of choline out of brain; however, the mechanism that mediates choline transport remains poorly understood. Dr. Villalobos will define the mechanism by which choroid plexus transports choline and will investigate how this mechanism might be modulated. The movement of choline by plexus can be most directly and effectively studied in tissues that are isolated and allowed to grow and reform a single sheet of interconnected cells. Using choline labeled with radioactive isotopes, Dr. Villalobos will determine how choline is transported into and out of the choroid plexus under different conditions. In this manner, for example, the dependence of choline transport on sodium and potassium can be determined. In addition, a specialized microscope will be used to visualize the internal scaffolding, or cytoskeleton, of the cell and to study how modulation of elements of the cytoskeleton may alter the ability of choroid plexus to transport choline. With these methods the effects of physical and chemical stress on choline transport will a lso be investigated. Determination of the cellular mechanism by which choline is transported from the brain to the blood by choroid plexus will provide the basic information necessary to probe further both the regulation of this specific transport process and the regulation of choline levels in the brain.
