From genes to neurons to brain

Molecular biological approaches have played a key role in our growing understanding of nervous system function in health and disease. However, coupling individual molecular events with the function of distributed neural systems involved in complex behaviors and neuropsychiatric diseases requires the integration of reductionist molecular work with systems neuroscience. Genetic and genomic methods can help provide a systems context for individual molecular changes and also serve as a bridge between human biology and animal or cell models. For example, once genes are identified as causal or susceptibility factors in human disease, the appropriate use of animal or in vitro models will play a key role in clarifying the structural and functional changes occurring at the cellular and neural systems levels. In contrast, when the underlying circuits are well connected to a particular conserved cognitive function or behavior, work in the animal models to define the molecular etiologies can be appropriately translated to humans. With regard to both of these approaches, the manuscripts in this supplement that highlight several presentations from the advanced course ‘Genes and Neurons’ (held in July 2004 at the University of Minho, Braga, Portugal) share a common theme of bridging the gulf between genes and behavior. These papers reflect an area of research that is emerging as one of broad interest to the neuroscience community, as it represents recent advances that bridge the gap between genes, brain and behavior, in many cases using animal models to help shed light on complex human behaviors or cognition and disorders that affect these processes. This ‘Genes and Neurons’ supplement provides a broad overview of this area, covering both fundamental and hot topics, ranging from the basics of mouse behavior and cognition (Sousa, Almeida and Wotjak), genetic approaches to common psychiatric diseases (van Belzen and Heutink), to the MAP kinase (MapK) pathway in memory (Davis and Laroche), the genetics and neurobiology of mental retardation (MR) (Dierssen and Ramakers), the molecular basis of circadian behavior (Oster), a molecular systems level approach to anxiety (Stoppel, Albrecht, Pape and Stork), chromatin remodeling and developmental disorders (Santos and Maciel) and Alzheimer ́ Dementia (Grazina and Oliveira). As such, this issue provides an extremely worthwhile and up to date review of these core topics in the molecular genetic basis of cognition and behavior for students and experts alike. In the comprehensively referenced ‘A hitchhiker’s guide to behavioral analysis in laboratory rodents’, Sousa and colleagues take on the difficult job of providing a template for approaching analysis of relevant behaviors in rats and mice. Several key points are worth noting. Sousa et al. emphasize the importance of using qualitative and quantitative strain differences in genetic mapping, and the challenges of moving from quantitative trait loci (QTLs) to genes, highlighting the development of more sophisticated and innovative analytic methods to facilitate these efforts. They focus on many critical practical issues that can impede proper assessment of behavior in mice, such as handling, training, stable routines and the failure to appreciate interstrain differences. Sousa et al. also appropriately caution us to be wary of overinterpreting molecular lesion studies, such as single-gene knockouts. Similar to anatomical lesion studies of the brain in developing animals, the functions being measured not only reflect the absence of a particular gene but also the potential consequences of environmental factors and molecular or behavioral systems’ adaptations to the insult, including the use of alternative strategies not relevant to normal development or function. Lastly, they provide a practical guide for the general assessment of behavior, physical features and cognition in mice. It is clear from this extensive guide that although some of the areas such as motor behavior and Genes, Brain and Behavior (2006), 5 (Suppl. 2), 1–4 # 2006 The Author Journal compilation # 2006 Blackwell Munksgaard