Calcium on the Up Supralinear Calcium Signaling in Central Neurons

calcium response also blocked the induction of LTP. quately explain the supralinearity of the calcium signal issue, 673–685. possibility was suggested by Schiller et al. (1998) on the press. basis of experiments in which they photolysed caged glutamate to produce a controlled level of postsynaptic activation, while simultaneously imaging the resulting calcium transient in dendritic spines. This approach reduces the concern that pharmacological manipulations Calcium on the Up: may also impact on the presynaptic neuron and allowed Schiller et al. (1998) to explore explicitly the role played by voltage-sensitive calcium channels. The experiments in Central Neurons reveal that nonlinear activation of voltage-sensitive calcium channels augments the synaptic signal when paired with an action potential and that the level of The pioneering experiments of the remarkable Russian augmentation is adequate to explain the calcium supra-behaviorist Ivan Pavlov firmly seeded the idea that asso-linearity. This approach does, however, have some limi-ciative interactions are a crucial element in the formation tations. For example, the authors take great care to of new memories. The precise neural basis for Pavlov's produce an electrical response following photolysis that mirrors a synaptically evoked excitatory postsynaptic observations are still, to this day, a matter of conjecture, but there is a keen recognition that the neural substrate potential (EPSP); however, in reality synaptically evoked responses are likely to arise from the sum of several of memory formation must involve some form of coincidence detection. That the NMDA receptor, which re-afferent inputs that are distributed at many sites across the postsynaptic cell. By contrast, photolysis yields an quires both glutamate binding and membrane depolar-ization to allow calcium influx, is capable of coincidence EPSP that arises within the restricted volume of the photolysed compound; such restricted release may well detection is not in doubt. Recently, however, a number of studies have raised the possibility that other elements produce a local depolarization that is considerably greater than that produced by any single synaptic event. of a neuron's intracellular machinery may also provide a mechanism for coincidence detection. There is, however, a third way in which supralinear calcium signals might be achieved. This involves the The first hint of a new coincidence detection mechanism in neurons came from Yuste and Denk (1995), in release of calcium from intracellular stores. The release of calcium from intracellular stores of central neurons a paper that introduced the use of two-photon micros-copy as a method for imaging …