Genetic Approach to the Study of the Nervous System

Beadle & Tatum ( 1) first showed that single step mutants may be used to elucidate complex physiological processes other than the mechanism of inheritance. These workers used mutants to analyze the biochemical pathways of the fungus Neuro­ spora. It has long been realized that mutants may also be helpful in the study of the nervous system (e.g. Ginsburg 2). However, the early approaches relied on spontaneously occurring mutations or on behavioral changes brought about by selective breeding. Benzer (3) proposed that, instead, single step mutations should be induced and appropriate mutants should be screened for use in the study of the nervous system. In the past few years, the technique of induced mutation has been gaining acceptance as potentially one of the most powerful tools available to neuro­ biologists. A wide range of organisms is presently being studied using this technique. Among them are the bacterium Escherichia coli (Adler 4, 5), the paramecium (Kung 6), the nematode (Ward 7), the fruitfty Drosophila (Benzer 3, 8; Pak et al 9; Ikeda & Kaplan 10; Heisenberg 11; Suzuki 12), the cricket (Bentley 13), and the mouse (Sidman et al 14, Wegmann et al 15). The rationale behind this approach lies in the fact that all physiological func­ tions ultimately depend upon genes. Genes, for example, are involved in regulating various physiological functions or in coding for polypeptides that are essential for various physiological processes. Therefore, a single gene mutation alters or removes a single structural or functional unit of a system, allowing the system to be studied in the absence of a single component at a time. The use of mutants seems particularly appropriate for the study of neuronal membrane processes, such as synaptic transmission, action potential generation, and sensory transduction. Because these are molecular processes, the possibility that mutations may be used to introduce specific perturbations at the molecular level is very appealing. In addition, genes are involved in directing the development of an