Alterations of Metabolites in the Nervous System

In neurosciences one may say, '"All roads lead to Rome. " It seems as though wherever one starts, the course of investigation leads to the same major ques­ tions about nervous system function and dysfunction. In thinking about what to write in this preface, it occurred to me that it might be best to deal with that with which I am most familiar and to trace to some extent my own '"road to Rome. '' As I look over my work of the last 37 years, it becomes clear to me that it can be epitomized as a search for patterns. What usually began as a single­ minded devotion to in-depth analysis of one or a small number of variables always has led to questions of how the results might relate to the whole living unit, whether it is cell, tissue, or organism. For a number of years after my discovery in the vertebrate central nervous system of -y-aminobutyric acid (GABA) and the enzyme which forms it, L­ glutamate decarboxylase (GAD), and the identification of GABA as a major inhibitory neurotransmitter by others, I felt that my laboratory, largely bio­ chemical, was wandering in the wilderness of the complexities of the vertebrate CNS without definitively coming to terms with problems related to GABAergic transmitter functions and the roles of GABA neurons in information processing.