Introduction to Mouse Transgenics and Behaviour
 
Richard Morris
R.G.M.Morris@ed.ac.uk
Department of Neuroscience, University of Edinburgh, UK

This lecture will serve two purposes: first, to outline the course structure and second, to explain the background to the four different behavioural projects that we will be conducting.

The course consists of lectures, project work and demonstrations. Transgenic mice are now used in many areas of neuroscience, but the area in which they were first introduced was the study of learning and memory. Accordingly, a high proportion of the lectures during the early part of the course will focus on relevant theoretical issues and the different types of transgenic mice that have been used. These include issues to do with multiple types of memory, long-term potentiation, hippocampal function (including its evolution), the NMDA receptor and the correlates of single-unit recording. Complementing these theoretical lectures will be a series of more methodological talks about different types of transgenic rodents, including gene overexpression, homologous recombination, conditional and inducible deletions, and site-directed mutagenesis. The second week of lectures is more diverse, taking us into important issues such as the ethics of experiments on living animals, models of human degenerative disease, genomic imprinting and models of cardiovascular disease. A principled framework for thinking about the use of genetic mutations will be presented and compared to classical interventionist techniques such as brain lesions and drugs.

The second part of the lecture will outline the four projects to be undertaken, all of which are pertinent to ongoing research here in Edinburgh. Each are genuine experiments under my Project License using mice harbouring mutations of PSD-95, the C-terminal of the NR2A receptor, a point mutation at codon 598 of the NMDAR1 receptor and overexpression of mutant APP. These animals and their littermate controls will be trained in the watermaze (using two different protocols), object and place recognition, and a relational learning task involving the social transmission of food preferences. The intellectual context and procedures involved will be described for each project, with an emphasis on the watermaze and the different training protocols that can be used in this single piece of apparatus.