Synaptic activation and membrane potential changes modulate the frequency of spontaneous elementary Ca2+ release...

In most neurons postsynaptic [Ca(2+)](i) changes result from synaptic activation opening voltage gated channels, ligand gated channels, or mobilizing Ca(2+) release from intracellular stores. In addition to these changes that result directly from stimulation we found that in pyramidal cells there are spontaneous, rapid, Ca(2+) release events, predominantly, but not exclusively localized at dendritic branch points. They are clearest on the main apical dendrite but also have been detected in the finer branches and in the soma. Typically they have a spatial extent at initiation of approximately 2 microm, a rise time of <15 ms, duration <100 ms, and amplitudes of 10-70% of that generated by a backpropagating action potential at the same location. These events are not caused by background electrical or synaptic activity. However, their rate can be increased by repetitive synaptic stimulation at moderate frequencies, mainly through metabotropic glutamate receptor mobilization of IP(3). In addition, their frequency can be modulated by changes in membrane potential in the subthreshold range, predominantly by affecting Ca(2+) entry through L-type channels. They resemble the elementary events ("sparks" and "puffs") mediated by IP(3) receptors and ryanodine receptors that have been described primarily in non-neuronal preparations. These spontaneous Ca(2+) release events may be the fundamental units underlying some postsynaptic signaling cascades in mature neurons.