Calcium: amplitude, duration, or location?

Calcium plays a role in long-term plasticity by triggering postsynaptic signaling pathways for both the strengthening (LTP) and weakening (LTD) of synapses. Since these are opposing processes, several hypotheses have been developed to explain how calcium can trigger LTP in some situations and LTD in others. These hypotheses fall broadly into three categories, based on the amplitude of calcium concentration, the duration of the calcium elevation, and the location of the calcium influx. Here we review the experimental evidence for and against each of these hypotheses and the recent computational models utilizing each. We argue that with new experimental techniques for the precise visualization of calcium and new computational techniques for the modeling of calcium diffusion, it is time to take a new look at the location hypothesis.