A role for Ca2+ stores in kainate receptor-dependent synaptic facilitation and LTP at mossy fiber synapses in the hippocampus

Compared with NMDA receptor-dependent LTP, much less is known about the mechanism of induction of NMDA receptor-independent LTP; the most extensively studied form of which is mossy fiber LTP in the hippocampus. In the present study we show that Ca²⁺-induced Ca²⁺ release from intracellular stores is involved in the induction of mossy fiber LTP. This release also contributes to the kainate receptor-dependent component of the pronounced synaptic facilitation that occurs during high-frequency stimulation. We also present evidence that the trigger for this Ca²⁺ release is Ca²⁺ permeation through kainate receptors. However, these novel synaptic mechanisms can be bypassed when the Ca²⁺ concentration is raised (from 2 to 4 mM), via a compensatory involvement of L-type Ca²⁺ channels. These findings suggest that presynaptic kainate receptors at mossy fiber synapses can initiate a cascade involving Ca²⁺ release from intracellular stores that is important in both short-term and long-term plasticity.