The genetic dissection of brain-behaviour relationships: An introduction to neurobehavioural genetics
Wim E. Crusio
Génétique, Neurogénétique et Comportement,
CNRS UPR 9074
Institut de Transgénose
3b, rue de la Férollerie
45071 Orléans Cedex 2
Send correspondence and proofs to: Dr. Wim E. Crusio at the above address.
Tel: + 33 2 38 25 79 74
Fax: + 33 2 38 25 79 79
Genetical methods are being used ever more frequently in behavioural neuroscience. The rapid growth of the field of behavioural neurogenetics is illustrated not only by a large outflow of scientific papers in some of the most prestigious journals in the field, but also by regular meetings, such as the yearly French-American Behavioural Neurogenetics Symposia, and the recent founding of its own specialised learned society, the International Behavioural and Neural Genetics Society, IBANGS. Although fashion undoubtedly plays some role in this, the main reason behind this is that genetical methods are very well suited to tackle problems that might be difficult or even impossible to address otherwise. The kind of problems addressed by behavioural neurogeneticists include general questions concerning which physiological mechanisms are implicated in the regulation of a certain behaviour or the causes of the sometimes considerable differences between normal healthy individuals, but also more specific problems concerning heritable neurological diseases. We may inquire, for instance, into the mechanisms that enable animals to learn, or ask ourselves which part of those mechanisms may show variability that might explain differences in learning capabilities between individuals, or search for the specific neurological causes of a learning deficit.
The present special issue on neurobehavioral genetics presents a number of state-of-the art examples of how some of these problems may be tackled using genetical methods. Among the latter, the oldest without any doubt is mutational analysis. This type of research has received an enormous impetus in recent years through the development of recombinant DNA methods that make targeted mutations possible, but as the contributions of Pflugfelder and Caston et al. show, the study of spontaneous mutations and mutations induced with more classical methods may contribute considerably to our understanding of neuronal processes underlying behaviour. Shaver et al. subsequently present a state-of-the-art genetic analysis of a naturally-occurring behavioural dimorphism in Drosophila larvae, whereas Steinlein presents an analysis of acetylcholine receptor mutations that are involved in epilepsy in humans.
The next set of articles (Gerlai et al., Lipp et al., Moechars et al., and Tremml et al.) provide illustrations of the application of modern gene-targeting methods to the genetic dissection of behavioural phenotypes. Gerlai et al. are interested in basic physiological principles underlying learning and memory processes, whereas the other contributions are more directed towards elucidating certain pathologies.
Human behaviour genetics has often limited itself to simply estimating those portions of the variance occurring in a population that might be attributable to either genetic or environmental causes. Although such data are perhaps of interest, by design this does not render any information about the underlying processes. Rijsdijk et al., in a study that will hopefully set an example, apply such classical, but highly sophisticated methods simultaneously to behavioural (IQ) and physiological (speed-of-information-processing) characters, showing how such variance-partitioning methods may be more fruitfully applied.
Next, Ammassari-Teule et al. and Gerlai show how a simple genetic strategy, comparison of inbred strains, may elegantly be used to provide information about basic brain mechanisms. In addition, their results contain a warning to those behavioural neuroscientists that are still doing research with genetically non-standardised animals: experimental results may be strain dependent.
Selective breeding has been part of the toolbox for the behavioural neurogeneticist ever since Tryon's classical study on maze learning in rats. Gariépy et al., Metten et al., and Aspide et al. show that this time-honoured method still has his place besides more flashy and fashionable molecular-genetic techniques. Finally, Roubertoux et al. present the results of a study concerning two genetically-distant inbred strains. The information obtained from this comparison can be used to design appropriate experiments to localise so-called Quantitative Trait Loci (QTL). Many QTL studies and putative localisations of QTLs have already been reported in the scientific literature. Some of these may, perchance, even be real. But, on closer examination, as yet the promise of the QTL method has not been fulfilled at all. Perhaps that the application of Advanced Intercross Lines, as advocated by Roubertoux et al., will finally lead not only to the localisation but also, and much more importantly, the identification of QTLs.
Most contributions to this special issue were selected from among the presentations to three meetings, the First, Second, and Third French-American Symposia on Behavioural Neurogenetics, that were held in 1995 (Richmond, VA, USA), 1996 (Washington, DC, USA), and 1997 (Orléans, France), respectively. Generous support from the Mission Scientifique et Technologique (Embassy of France, Washington, DC, USA), the National Institute of Mental Health (NIH, Rockville, MD, USA), and the Centre National de la Recherche Scientifique (Orleans, France), made these meetings possible.