Amplification of calcium signals at dendritic spines provides a method forCNS quantal analysis

It has been proposed that the small volume of a dendritic spine can amplify Ca2+ signals during synaptic transmission. Accordingly, we have performed calculations to determine whether the activation of N-methyl-D-aspartate (N MDA) type glutamate receptors during synaptic transmission results in signi ficant elevation in intracellular Ca2+ levels, permitting optical detection of synaptic signals within a single spine. Simple calculations suggest tha t the opening of even a single NMDA receptor would result in the influx of similar to 310 000 Ca2+ ions into the small volume of a spine, producing ch anges in Ca2+ levels that are readily detectable using high affinity Ca2+ i ndicators such as fura-2 or fluo-3. Using fluorescent Ca2+ indicators, we h ave imaged local Ca2+ transients mediated by NMDA receptors in spines and d endritic shafts attributed to spontaneous miniature synaptic activity. Deta iled analysis of these quantal events suggests that the current triggering these transients is attributed to the activation of < 10 NMDA receptors. Th e frequency of these miniature synaptic Ca2+ transients is not randomly dis tributed across synapses, as some synapses can display a > 10-fold higher f requency of transients than others. As expected for events mediated by NMDA receptors, miniature synaptic Ca2+ transients were suppressed by extracell ular Mg2+ at negative membrane potentials; however, the Mg2+ block could be removed by depolarization.