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Synaptic plasticity appears to be triggered by changes in intracellular Ca²⁺. Although it seems likely that LTP is triggered by large elevations of Ca²⁺ and that LTD is triggered by more moderate Ca²⁺ elevations, these changes have never been observed at synapses known to be active and to be undergoing synaptic modification. This raises the technical question of how we could follow the function of individual synapses. Our long-term goal is optical quantal analysis, the determination of the quantal analysis parameters, p and q, at an identified synapse. Towards that end we are using confocal microscopy of individual synapses to study changes in Ca²⁺ and Na⁺. Our initial work, done in collaboration with Robert Malinow and Arthur Konnerth has shown how Ca²⁺ signals at individual synapses can be measured during single synaptic events. This approach needs to be further developed so that accurate measures of p and q can be made. We would then hope to induce LTP or LTD, determine how Ca²⁺ changes during induction, and finally see how p and q are altered.