cortex

Project number:

403

Project title:

The role of CaMKII in plasticity of dendritic spines

Project supervisor:

Project description:

Many reports in the field of LTP and LTD have shown that spine morphology is highly plastic with thin spines becoming larger (development of mushroom spines) with LTP and smaller with LTD. We have recently demonstrated that the percentage of mushroom spines found in the dendritic tree does not change over development across the dendritic tree during development (De Simoni et al, 2003) but that the proportion is highly pathway specific (manuscript under review). We have developed techniques in organotypic slices which we can differentiate spines which receive their input from specific input pathways and hence compare spines in a CA! cell which receive input from Schaffer collaterals, perforant path or other CA1 cells.

The overall distribution of spines is very similar to that in acute slices or tissue fixed in vivo with mushroom spines staying at <20% throughout development. However if we differentiate for different pathways we find that Schaffer collaterals start with few if any mushroom spines but over the first two weeks in culture develop to have as many ad 50% mushroom spines while they remain rare in the other two pathways tested (<10%).

This project will use patch clamp and confocal microscopy to study the homeostatic interactions of these different pathways and the role of ?-Calcium calmodulin kinase (?CaMKII) in allowing this pathway specificity to develop.

Mice which have a mutation (T286A) in their ?-Calcium calmodulin kinase (?CaMKII) have normal CamKII function except that they lack autophosphosphorylation of the enzyme. This results in a lack of long term potentiation and an inability to learn in a swim maze. Organotypic slices will be made from mutant and wild type mice and the morphology and development of their spines compared under different conditions.

Possible cortex partners for rotation:

Oslo. Following up the differences assessed with confocal microscopy with EM analysis
Helsinki. The role of GABAergic signalling in such homeostasis.