A Role for Ca2+ Stores in Kainate Receptor-Dependent Synaptic Facilitation and LTP at Mossy Fiber Synapses in the Hippocampus

Abstract

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.

Calcium release via activation of presynaptic IP3 receptors contributes to kainate-induced IPSC facilitation in rat neocortex

“…These results suggest that Ca 2+ entry via Ca 2+ -permeable KARs is involved. The facilitation of GABAergic transmission upon KAR activation was blocked after inhibition of endosomal Ca 2+ -ATPase-mediated Ca 2+ uptake with thapsigargin, suggesting a role for intracellular stores in the KAR mediated facilitation of GABA release, as reported for hippocampal neurons (Lauri et al, 2003). The inability of high concentrations of ryanodine, which has an antagonist action by completely closing the release channels (Meissner, 1994;Masumiya et al, 2001), to block KAR-induced changes indicated that RyRs are not involved.…”

“…Release of Ca 2+ from internal stores is mediated both by RyRs and IP3Rs. Ryanodine sensitive stores have been previously reported to be involved in KA facilitation in some studies (Lauri et al, 2003) but not others (Breustedt and Schmitz, 2004). Bath application of 100 µM ryanodine, a concentration that blocks RyRs (Ehrlich et al, 1994;Liu et al, 2005), did not affect facilitation of evoked IPSC amplitudes (Fig.…”

“…It is well established that cortical networks are modulated via dopaminergic (Bjorklund and Lindvall, 1984), noradrenergic (Kawaguchi and Shindou, 1998) and cholinergic (Mesulam et al, 1983) inputs. Control over Neurotransmitter release can be altered by calcium release from intracellular stores (Meldolesi, 2001;Rose and Konnerth, 2001;Lauri et al, 2003;Simkus and Stricker, 2002). Such liberation from the endoplasmic reticulum (ER) is mediated through RyRs and IP3Rs (Berridge, 1998).…”

Use-dependent amplification of presynaptic Ca 2+ signaling by axonal ryanodine receptors at the hippocampal mossy fiber synapse

“…Since these responses were blocked by ryanodine, the authors suggested that concerted release of multiple quanta was evoked by nicotine possibly through local Ca 2ϩ release from presynaptic ryanodine-sensitive stores. It was also reported that ryanodine suppressed the induction of presynaptic forms of long-term potentiation (LTP) unique to this synapse (33). Taking together, it was strongly suggested that functional ryanodine-sensitive Ca 2ϩ stores existed in presynaptic sites of the mossy fiber-CA3 synapse.…”

Ca 2+ stores and use-dependent facilitation of presynaptic Ca 2+ signaling

“…The study uses a bulkloaded cell-permeable Ca 2ϩ indicator to monitor intracellular Ca 2ϩ and examines postsynaptic responses with an extracellular electrode. Previously, the ryanodine receptor-dependent facilitation of presynaptic Ca 2ϩ signals was demonstrated in individual, identified MF boutons traced from the granule cell soma (2), and the corresponding facilitation of postsynaptic responses was reported in individual CA3 pyramidal cells (3).…”