The role of presynaptic calcium at ageing synapses

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Ageing leads to a decline in our ability to remember. Some people age relatively well whereas others are very severely affected. It was originally thought that the age-related decline in cognitive function was due to a loss of cells within the brain but it is now thought that natural ageing is distinct from neurodegenerative conditions, such as Alzheimer's disease, where cell death and structural changes are very apparent. In regions of the brain responsible for memory formation and retention, such as the prefrontal cortex and hippocampus, relatively subtle changes in the connections between cells may account for age-related deficits in memory formation. Calcium plays a fundamental role in controlling many functions within cells including communication between cells. Changes in the strength of signalling between cells are thought to provide a mechanism for memory formation and these are highly dependent up calcium. We have developed a genetically modified mouse that expresses a sensor that is capable of measuring calcium. The sensor is located at the specialised terminals (synaptic terminals) of excitable cells within the brain that are responsible for releasing the chemical transmitters that transfer information from cell to cell. In this application, we wish to use imaging techniques to measure the changes in calcium within synaptic terminals during normal activity within the hippocampus and compare them to signalling in aged animals that display an age-related decrease in memory. In so doing, we hope to understand the mechanisms that are responsible for age-related decreases in brain function.