This project began when I was in my first neuroscience post-doc, doing a Wellcome Training Fellowship in Mathematical Biology with Julian Jack in Oxford. Julian's lab had done a lot of work on synaptic physiology, in particular developing quantal analysis as a tool to examine central synapses. The physiology underlying quantal analysis is the fact that neurons are generally connected by more than one terminal. When the presynaptic neuron fires an action potential, packets - quanta - of neurotransmitter may be released from all, some or none of these terminals. If each packet of neurotransmitter contributes a similar amount to the postsynaptic depolarisation, then a histogram of the effect produced by each presynaptic action potential will have several peaks, corresponding to the release of 0, 1, 2 ... quanta of neurotransmitter. In principle, this histogram can then be analysed to estimate the effect caused by each quantum, and the probability that a quantum will be released from a terminal given an action potential. In practice, this depends critically on things like whether each quantum really does have a very similar postsynaptic effect, whether the release probability is the same at all terminals, whether these quantities are constant over time and so on. Julian's lab had already developed a lot of sophisticated tools for quantal analysis, and I took this further, developing a still more elaborate fitting algorithm to extract the quantal parameters, and also a battery of statistical tests to decide whether the resulting model of the synapse was adequate. There's quite a lot of sceptism as to how far quantal analysis can be trusted in the central nervous system (as opposed to at the neuromuscular junction, where it was originally developed), so these tests were critical in convincing people that our results were reliable. Neil Hardingham, the first author, who was a Ph.D. student and post-doc in Julian's lab when I was there, used these techniques to examine how the quantal parameters change as a function of extracellular calcium. He was able to show that calcium depletion, as well as reducing release probability, also reduces quantal size. Since calcium levels drop as neurons become active, this represents a novel mechanism for regulating information transfer between neurons.