Kamiya H, Umeda K, Ozawa S, Manabe T. Presynaptic Ca2+ entry is unchanged during hippocampal mossy fiber long-term potentiation. J Neurosci 22: 10524-10528

Department of Applied Biology, Kyoto Institute of Technology, Kioto, Kyoto, Japan
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 01/2003; 22(24):10524-8.
Source: PubMed


The hippocampal mossy fiber (MF)-CA3 synapse exhibits NMDA receptor-independent long-term potentiation (LTP), which is expressed by presynaptic mechanisms leading to persistent enhancement of transmitter release. Recent studies have identified several molecules that may play an important role in MF-LTP. These include Rab3A, RIM1alpha, kainate autoreceptor, and hyperpolarization-activated cation channel (I(h)). However, the precise cellular expression mechanism remains to be determined because some studies noticed essential roles of release machinery molecules, whereas others suggested modulation of the ionotropic processes affecting Ca2+ entry into the presynaptic terminals. Using fluorescence recordings of presynaptic Ca2+ in hippocampal slices, here we demonstrated that MF-LTP is not accompanied by an increase in presynaptic Ca2+ influx during an action potential. Whole-cell recordings from CA3 neurons revealed long-lasting increases in mean frequency, but not mean amplitude, of miniature EPSCs after the high-frequency stimulation of MFs. These data indicate that the presynaptic expression mechanisms responsible for enhanced transmitter release during MF-LTP involve persistent modification of presynaptic molecular targets residing downstream of Ca2+ entry.

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    • "The role of Ca 2+ in the mediation of the effects of KAR activation on release facilitation and LTP at MF–CA3 synapses has been subject of some debate and, indeed controversy. Thus, while some studies have suggested that a permeation of Ca 2+ through KARs and subsequent Ca 2+ -induced Ca 2+ release from internal stores is a requirement for short-term and long-term plasticity at MF–CA3 synapses (Lauri et al. 2003; Scott et al. 2008), others find that Ca 2+ plays no role in the regulation (Kamiya et al., 2002), and yet others suggest that KAR activation actually decreases Ca 2+ influx at this synapse to effect synaptic inhibition (Kamiya and Ozawa 1998, 2000). At present, therefore, it is not clear whether or not the increase of synaptic glutamate release mediated by presynaptic KARs at the MF-synapse involves Ca 2+ activity. "
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    ABSTRACT: J. Neurochem. (2012) 122, 891–899. Presynaptic kainate receptors (KARs) modulate the release of glutamate at synapses established between mossy fibers (MF) and CA3 pyramidal cells in the hippocampus. The activation of KAR by low, nanomolar, kainate concentrations facilitates glutamate release. KAR-mediated facilitation of glutamate release involves the activation of an adenylate cyclase/cyclic adenosine monophosphate/protein kinase A cascade at MF–CA3 synapses. Here, we studied the mechanisms by which KAR activation produces this facilitation of glutamate release in slices and synaptosomes. We find that the facilitation of glutamate release mediated by KAR activation requires an increase in Ca2+ levels in the cytosol and the formation of a Ca2+–calmodulin complex to activate adenylate cyclase. The increase in cytosolic Ca2+ underpinning this modulation is achieved, both, by Ca2+ entering via Ca2+-permeable KARs and, by the mobilization of intraterminal Ca2+ stores. Finally, we find that, congruent with the Ca2+–calmodulin support of KAR-mediated facilitation of glutamate release, induction of long-term potentiation at MF–CA3 synapses has an obligate requirement for Ca2+–calmodulin activity.
    Full-text · Article · Jun 2012 · Journal of Neurochemistry
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    • "To obtain independent evidence in support of this interpretation, additional experiments examined spontaneous release of glutamate in the presence of tetrodotoxin (TTX), which eliminates action potentials; the action potential-independent release of glutamate detected as mEPSCs measures random mono-quantal release of glutamate. The occurrence of increased frequency without change in amplitude of mEPSCs accompanying mf-LTP provides additional evidence of increased release of glutamate and a presynaptic locus of expression of mf-LTP (Kamiya et al., 2002). mEPSCs in CA3 pyramids (Jonas et al., 1993) were examined in whole cell recordings in the presence of tetrodotoxin (1 μM). "
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    ABSTRACT: The presence of zinc in glutamatergic synaptic vesicles of excitatory neurons of mammalian cerebral cortex suggests that zinc might regulate plasticity of synapses formed by these neurons. Long-term potentiation (LTP) is a form of synaptic plasticity that may underlie learning and memory. We tested the hypothesis that zinc within vesicles of mossy fibers (mf) contributes to mf-LTP, a classical form of presynaptic LTP. We synthesized an extracellular zinc chelator with selectivity and kinetic properties suitable for study of the large transient of zinc in the synaptic cleft induced by mf stimulation. We found that vesicular zinc is required for presynaptic mf-LTP. Unexpectedly, vesicular zinc also inhibits a form of postsynaptic mf-LTP. Because the mf-CA3 synapse provides a major source of excitatory input to the hippocampus, regulating its efficacy by these dual actions, vesicular zinc is critical to proper function of hippocampal circuitry in health and disease.
    Full-text · Article · Sep 2011 · Neuron
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    • "Furthermore, previous study demonstrated that forskolin, which raise intracellular cyclic AMP levels and reportedly cause mossy fiber synaptic enhancement (Weisskopf et al., 1994), didn't affect F value significantly (Kamiya et al., 2002).These results exclude the possibility that caffeine-induced presynaptic Ca 2+ increase involves inhibiting effects of caffeine on A1 receptors and phosphodiesterase. Instead, Ca 2+ release from presynaptic ryanodine-sensitive stores likely mediates the action of caffeine. "
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    ABSTRACT: Caffeine robustly enhances transmitter release from the hippocampal mossy fiber terminals, although it remains uncertain whether calcium mobilization through presynaptic ryanodine receptors mediates this enhancement. In this study, we adopted a selective adenosine A1 blocker to assess relative contribution of A1 receptors and ryanodine receptors in caffeine-induced synaptic enhancement. Application of caffeine further enhanced transmission at the hippocampal mossy fiber synapse even after full blockade of adenosine A1 receptors. This result suggests that caffeine enhances mossy fiber synaptic transmission by two distinct presynaptic mechanisms, i.e., removal of A1 receptor-mediated tonic inhibition and ryanodine receptor-mediated calcium release from intracellular stores.
    Preview · Article · Jul 2011 · Neuroscience Research
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