projects

Projects

The course includes four Research Projects and a series of Demonstrations. The 16 students worked in groups of 4 students per project. Each of the projects used transgenic or mutant mice that are of interest to ongoing research here in Edinburgh. As outlined in the Introductory Lecture, this experimental work is licenced by the U.K.Home Office and we cannot undertake experiments purely for teaching purposes. A brief summary of the projects and their results is as follows:

Project A	*Place navigation in PDAPP (‘Athena’) mice.* Jukka Puoliväli Angel Barco Abdel Ennaceur Thomas Lemberger Games et al (1995) reported that mice overexpressing mutant APP display age-related plaque formation. There has, to date, been relatively little behavioural work done on these mice – either before they show plaques or afterwards. The object of this project was to explore whether these animals would show an impairment of place navigation (spatial reference memory) and reversal learning in the watermaze. The animals we used were born in October/November of 1998 and so should have a reasonable accumulation of amyloid plaques. The results of a simple watermaze expertiment consisting of cue-learning, place reference memory, reversal learning and probe tests revealed a clear trend towards a deficit in the PDAPP mice relative to the littermate controls, particularly in reversal learning. However, the group sizes were too small to reach statistical significance.
Project B	*Object and place recognition in N598Rneo mice* Konstantin Radyushkin Claudia F. Plappert Virginie Biou Silvia Lommel Dr Ralf Schoepfer, of University College London, has recently developed mice harbouring a point mutation at codon 598 of NR1 rendering the NMDA receptor channel impermeable to Ca²⁺. Some limited work has been done with these mice on LTP, but no behavioural work to date. This project will explore whether these animals can remember a recently explored object, and for how long, and can remember a location at which an object has been presented in a simple arena. Memory is displayed in terms of the animal’s reaction to novelty. The outcome can, at best be described as disappointing. The key problem was that the object recognition test is very sensitive to noise and other disturbances and the conditions of testing, with up to 4 persons in the testing room, were far from ideal. The mice either ignored the objects for long periods or, in some cases, behaved at chnace (visiting the familiar and new objects equally often). Some instability of choice behaviour was also observed in the sample phase. However, this set-back may have been a blessing in disguise as the group developed a set of key recommendations for future testing, based in part on seeing the video presentations of the elevated plus-maze demonstration.
Project C	*Delayed matching to place in NR2deltaC mice* Osnat Cohen Aapo Honkanen Ozlem Yilmaz Björn Brembs Preliminary work in Edinburgh has established that animals with a deletion of the C-terminal region of the NR2 sub-unit of the NMDA receptor show impaired recognition memory, but no impairment in place navigation (Asfal, in preparation). As the recognition task is single-trial, and place navigation multi-trial, it seemed worth exploring whether one-trial spatial learning would be impaired or not. Accordingly, this project involved training the animals on the delayed matching-to-place (DMP) protocol in the watermaze and testing memory at two delay intervals. This project ran smoothly but the savings between trials 1 and 2 of the DMP task which are so evident in testing with rats are less easily seen in mice. After the first three familiarisation days, there was little sign of major savings and the group therefore abandoned testing at two memory delays. Instead, they explored the effects of additional cues and extended training on the basic task. When averaged across nice days of testing, a clear within-day improvement could be seen, but it seems the task protocol requires further development to be generally useful.
Project D	*Social Transmission of Food Preferences in PSD-95 mutant mice* Sulev Kôks Janos P. Kiss Jenni Jonasson Margaret I. McLean Migaud et al (1998) reported that PSD-95 mutant mice show a shift in the frequency function determining LTP. At most tetanisation frequencies, enhanced LTP is displayed. However, these animals also show a very severe impairment in place navigation and, in Asfal’s recent M.Sc project work, object and place recognition is impaired. The purpose of this project is to examine another form of memory thought to depend on intact hippocampal function – the social transmission of food preferences. This is an example of what Bunsey and Eichenbaum (1995) call relational-learning, but it does not involve spatial learning. A pilot experiment was first conducted using C57/BL6 mice – this ran very well and produced a striking preference in the ‘observer’ mice for the food eaten earlier by the ‘demonstrator’ mice. In the ‘real’ experiment that followed, the PSD95 mice were found to be hypersensitive to food deprivation – at least under the conditions of our testing. Consequently, the test could not be completed satisfactorily in the mutants although the littermate controls showed the expected social transmission effect.