UC San Diego

The brain is a complex organ, responsible for our intelligence, awareness, and ability to sense and interact with the world around us. In order to understand how the brain performs such advanced computations, it is important to elucidate the circuitry of the brain and to determine how that circuitry underlies its function. In practical terms, solving this problem requires targeted perturbations of specific neuron types. Such a strategy will allow for comparisons of brain function in intact versus partially handicapped brains. Chapter I of this dissertation outlines this problem, and explains how genetic strategies for targeting individual cell types can advance our understanding of brain function. Examples of such strategies, along with a discussion of the advantages and disadvantages of each, are outlined in Chapter II. Chapter III presents novel data describing a particular genetically-based strategy, termed the allatostatin receptor/ allatostatin (AlstR/AL) system, in detail. Using adeno-associated viral vectors to express the AlstR/AL system in vivo, we demonstrate that it is an effective method for quickly and reversibly inactivating neurons in a variety of mammalian species. Such a method can be applied to investigate the role of individual cell types in neural circuits and overall brain function. The applications of the AL/AlstR method, along with a discussion of technical hurdles that were overcome to develop the method, are discussed in Chapter IV