Genetic dissection of neural circuits and behavior in Mus musculus

One of the major challenges in the field of neurobiology is to elucidate the molecular machinery that underlies the formation and storage of memories. For many decades, genetic studies in the fruit fly (Drosophila melanogaster) have provided insight into the role of specific genes underlying memory storage. Although these pioneering studies were groundbreaking, a transition to a mammalian system more closely resembling the human brain is critical for the translation of basic research findings into therapeutic strategies in humans. Because the mouse (Mus musculus) shares the complex genomic and neuroanatomical organization of mammals and there is a wealth of molecular tools that are available to manipulate gene function in mice, the mouse has become the primary model for research into the genetic basis of mammalian memory. Another major advantage of mouse research is the ability to examine in vivo electrophysiological processes, such as synaptic plasticity and neuronal firing patterns during behavior (e.g., the analysis of place cell activity). The focus on mouse models for memory research has led to the development of sophisticated behavioral protocols capable of exploring the role of particular genes in distinct phases of learning and memory formation, which is one of the major accomplishments of the past decade. In this chapter, we will give an overview of several state of the art genetic approaches to study gene function in the mouse brain in a spatially and temporally restricted fashion.