Priming of intracellular calcium stores in rat CA1 pyramidal neurons

Repetitive synaptic stimulation evokes large amplitude Ca²⁺ release waves from internal stores in many kinds of pyramidal neurons. The waves result from mGluR mobilization of IP₃ leading to Ca²⁺-induced Ca²⁺ release. In most experiments in slices, regenerative Ca²⁺ release can be evoked for only a few trials. We examined the conditions required for consistent release from the internal stores in hippocampal CA1 pyramidal neurons. We found that priming with action potentials evoked at 0.5–1 Hz for intervals as short as 15 s were sufficient to fill the stores, while sustained subthreshold depolarization or subthreshold synaptic stimulation lasting from 15 s to 2 min was less effective. A single episode of priming was effective for about 2–3 min. Ca²⁺ waves could also be evoked by uncaging IP₃ with a UV flash in the dendrites. Priming was necessary to evoke these waves repetitively; 7–10 spikes in 15 s were again effective for this protocol, indicating that priming acts to refill the stores and not at a site upstream to the production of IP₃. These results suggest that normal spiking activity of pyramidal neurons in vivo should be sufficient to maintain their internal stores in a primed state ready to release Ca²⁺ in response to an appropriate physiological stimulus. This may be a novel form of synaptic plasticity where a cell's capacity to release Ca²⁺ is modulated by its average firing frequency.