A tool for synthesis

Handbook of Molecular-Genetic Techniques for Brain and Behavior Researchedited by W.E. Crusio and R.T. GerlaiElsevier, 1999. $177.50 (994 pages)ISBN 444 50239 4The ‘Decade of the Brain’, which came to a close a few months ago, was witness to remarkable growth and progress in the neurosciences. Perhaps one of the most characteristic breakthroughs of the decade was the development of methods in which model systems for physiological and behavioral investigations became molecularly and genetically tractable and vice versa. Powerful new techniques allow integrative investigations of the action of genes in the development and physiology of the brain that are pertinent to behaviors as diverse as drug addiction and learning and memory. This multi-disciplined approach, essential for a unifying synthesis of neural function, is necessary to tame the flood of information generated by the genome projects and place it within a physiological context.The Handbook of Molecular-Genetic Techniques for Brain and Behavioral Research is the thirteenth volume in the distinguished series Techniques in the Behavioral and Neural Sciences. These volumes focus on specific experimental topics and approaches within a particular discipline of neuroscience. However, thirteen is a charm, as the current volume is the first to approach brain and behavior research in a truly multi-disciplinary fashion. Although the book focuses on molecular and genetic techniques, it opens with a highly informative and unique section on neurobehavioral informatics and experimental design, whereas the section on the ethical considerations of behavioral genetics in animal models and ‘psychiatric genetics’ in humans is the most fitting epilogue. The breadth of the leading and penultimate sections is reflective of the range of topics covered in the remaining sections. These focus on molecular-genetic techniques for the identification of novel genes that are essential for neuronal function, and transgenic methods to manipulate such genes and understand their role. The following two sections are the most wide-ranging and highly integrative. Ethological approaches are integrated with molecular biology to address behavioral phenotypes in rodents, ranging from maternal behaviors to learning and memory. This serves as a comprehensive introduction to the section focusing on the use of animal systems to model human neurobehavioral disorders ranging from schizophrenia to Downs syndrome and Alzheimer's disease.Conceptually, the manual is masterfully organized with a presentation of basic issues heading each section. The specific focus of each section is addressed by presenting new molecular, genetic, behavioral and mathematical techniques, alongside novel adaptations of older ones. Finally, specific examples of applications of these techniques amply illustrate their power to address these issues in brain function and behavior. One of the main assets of the book is that it is written by leading authors in their respective fields, who have either developed or used the techniques presented. The techniques are presented clearly, outlining their applicability and useful features but also warning against the specific problems and pitfalls of each method. The inevitable degree of repetition in describing basic techniques, such as PCR and the generation of transgenics, can actually be helpful because it shows the variations in approaching the same task from different laboratories that have established expertise. However, a few more illustrations and diagrams would have been helpful, especially with the mathematically oriented subjects. The main thrust of the book is the multiplicity of molecular and genetic strategies, tools and approaches for understanding a wide range of normal and pathological behaviors and as such this fully justifies the title of the preface: ‘behavioral neurogenetics, the new synthesis’.Unquestionably, Drosophila has been the leader in the effort to link behaviors and the activity of single genes with the isolation of the first ‘learning and memory’ mutant. This research resulted in the identification and characterization of the affected gene dunce in the 1970s. To date, multiple such genes have been identified and characterized in the fruit fly following the development of powerful and efficient screening techniques and strategies to characterize the affected genes. Because the Drosophila genome has now been sequenced, this insect is expected to be essential in understanding the behavioral role of many genes. However, although it is a powerful genetic system, Drosophila is not included in the section that focuses on searching for new genes. Moreover, although Drosophila transgenesis has been an essential research tool for decades, it is only briefly included in the transgenic section of the manual. Because the book focuses mainly on rodent models perhaps this is not a surprise, all the same it is still rather disappointing. Moreover, any reference to the entire field of biological rhythms and molecular clocks, an area of recent significant progress and one of the pillars of behavioral and molecular neurogenetics, is conspicuously absent!Nevertheless, the book epitomizes the coming of age of molecular and genetic approaches in the understanding of brain function. The greatest strength of the book is that it speaks the language of the experimental psychologist that wants to explore molecular and genetic approaches, and at the same time communicates well with the molecular geneticist searching for behavioral avenues to investigate a phenotype, or establish a model system. For the afficionados, this book offers a reference volume that underscores the current trend for a synthesis of behavioral, molecular and genetic approaches with which to understand the link between genes and molecules, neuronal activity and behavior. As such, this manual should be required reading for all newcomers to the field.(This review originally appeared in the February issue of Trends in Neurosciences.)