Genetic Studies on Behavior

Animal behavior is one of the most complex phenomena in biology. Understanding the cellular and molecular basis of behavior is one of the critical issues in modern neuroscience. The emergence of molecular neurogeneticsneurogenetics was driven mainly by the idea that genes regulate the neural circuit and behavior and, therefore, can be dissected by genetic analysis. Genetic studies of behavior in Drosophila pioneered by Seymour BenzerSeymour Benzer and colleagues in the 1960s laid the foundation for molecular neurogenetics. This chapter will discuss how genetic approaches contributed to dissecting the mechanism underlying circadian rhythmcircadian rhythm behavior. First, experimental paradigms for separating behavioral mutants will be introduced. The isolation and genetic analysis of the first clock mutantclock mutant period (per) are described. We will then discuss molecular cloning of the per gene and its expression. Expression levels of per RNA and protein fluctuate according to the day-night cycle, consistent with its role in a circadian clock. The per studies are followed by the finding of timeless (tim) that encodes the binding partner of Per. Per and Tim form a protein complex to enter the nucleus, leading to the feedback inhibition of their own mRNA expression. The regulation of Per and Tim provides a basis for the circadian rhythmic behavior. We will discuss and compare molecular models for clocks in Drosophila and mammals.