Project number:
401
Project title:
The role of LTP in learning and memory
Project supervisor:
Frances Edwards
Project description:
Long term potentiation (LTP) is the best cellular model we have for a molecular basis of learning and memory but demonstrating its role physiologically has been elusive. By comparing mutant mice which have no LTP with their wild type littermates we aim to find differences which might give clues to what LTP is really doing in vivo. We have chosen to use mice which have a point mutation in the ? isoform of their Ca2+ Calmodulin-dependent kinase II (?CaMkII) at the autophosphorylation site 286 (T286A). These mice have no LTP in the CA1 region and do not learn in a Morris hidden platform water maze. We use environmental enrichment to enhance the use of hippocampal dependent learning so that we can compare differences in non enriched and enriched wild type and mutant mice. Using patch clamp in brain slices to measure individual synaptic strengths and confocal imaging to study details of morphology, we find that environmental enrichment causes changes in the mutant mice which are not seen in the wild type mice.
These findings (soon to be submitted for publication) suggest the hypothesis that learning is carried in the hippocampus by processes similar to long term depression (LTD) but that once memory is consolidated elsewhere (presumably in cortex these changes must be reversed by LTP in order for the hippocampal pathways to be available for further processing. Such reversal would not occur in the mutant mice lacking LTP.
This project will go on to test this hypothesis further. It leads to a variety of predictions both in terms of electrophysiology and morphology which can be tested in the London lab.
Possible cortex partners for rotation:
Denise Manahan-Vaughan (Bochum) Predictions can be made which will be tested using behavioural paradigms of learning and memory.
Ole Petersen (Oslo) EM comparisons of the glutamatergic synapses of the four groups may reveal differences essential to learning and memory
The cortex Partners: Berlin, Bochum,
Helsinki, London, Oslo,
Prague, Stockholm, Zurich
