The Experts below are selected from a list of 315 Experts worldwide ranked by ideXlab platform
Roger A. Nicoll - One of the best experts on this subject based on the ideXlab platform.
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Glutamate and y-aminobutyric ac depression at Mossy Fiber synaps
2016Co-Authors: Kaspar E. Vogt, Roger A. NicollAbstract:Mossy Fiber synapses form the major excita- tory input into the autoassociative network of pyramidal cells in the CA3 area of the hippocampus. Here we demonstrate that at the Mossy Fiber synapses, glutamate and y-aminobutyric acid (GABA) act as autaptic and heterosynaptic presynaptic inhibitory transmitters through metabotropic glutamate re- ceptors (mGluRs) and GABAB receptors, respectively. Both GABAB receptors and mGluRs are activated through spillover from adjacent synapses. We demonstrate that glutamate spillover caused by brief tetanic activation of Mossy Fiber terminals remains intact at physiological temperatures. The activation of GABAB receptors increased the threshold for Mossy Fiber long-term potentiation (LTP), whereas activation of mGluRs did not have such an effect. We speculate that this heterosynaptic depression provides the Mossy Fiber synapses with a mechanism to efficiently shape input patterns into CA3, increasing the sparseness of the Mossy Fiber signal and enhancing the capacity and performance of the CA3 associa- tive network. The increase in LTP threshold through activa- tion of presynaptic inhibitory receptors imparts a piesynoptic associative nature to Mossy Fiber LTP.
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presynaptic kainate receptors impart an associative property to hippocampal Mossy Fiber long term potentiation
Nature Neuroscience, 2003Co-Authors: Dietmar Schmitz, Joerg Breustedt, Jack R Mellor, Roger A. NicollAbstract:Hippocampal Mossy Fiber synapses show an unusual form of long-term potentiation (LTP) that is independent of NMDA receptor activation and is expressed presynaptically. Using receptor antagonists, as well as receptor knockout mice, we found that presynaptic kainate receptors facilitate the induction of Mossy Fiber long-term potentiation (LTP), although they are not required for this form of LTP. Most importantly, these receptors impart an associativity to Mossy Fiber LTP such that activity in neighboring Mossy Fiber synapses, or even associational/commissural synapses, influences the threshold for inducing Mossy Fiber LTP. Such a mechanism greatly increases the computational power of this form of plasticity.
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Hippocampal Mossy Fiber LTP is independent of postsynaptic calcium
Nature Neuroscience, 2001Co-Authors: Jack R Mellor, Roger A. NicollAbstract:We tested a proposal that postsynaptic calcium and metabotropic glutamate receptors (mGluRs) are involved in the induction of hippocampal Mossy Fiber long-term potentiation (LTP)1. We found that blockade of mGluRs with a range of antagonists, or dialysis of the postsynaptic cell with 50 mM BAPTA, had no effect on Mossy Fiber LTP. Therefore, we concluded that Mossy Fiber LTP is independent of postsynaptic calcium.
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The actions of synaptically released zinc at hippocampal Mossy Fiber synapses.
Neuron, 2000Co-Authors: Kaspar E. Vogt, Jack R Mellor, Gang Tong, Roger A. NicollAbstract:Abstract Zn 2+ is present at high concentrations in the synaptic vesicles of hippocampal Mossy Fibers. We have used Zn 2+ chelators and the mocha mutant mouse to address the physiological role of Zn 2+ in this pathway. Zn 2+ is not involved in the unique presynaptic plasticities observed at Mossy Fiber synapses but is coreleased with glutamate from these synapses, both spontaneously and with electrical stimulation, where it exerts a strong modulatory effect on the NMDA receptors. Zn 2+ tonically occupies the high-affinity binding site of NMDA receptors at Mossy Fiber synapses, whereas the lower affinity voltage-dependent Zn 2+ binding site is occupied during action potential driven–release. We conclude that Zn 2+ is a modulatory neurotransmitter released from Mossy Fiber synapses and plays an important role in shaping the NMDA receptor response at these synapses.
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Glutamate and γ-aminobutyric acid mediate a heterosynaptic depression at Mossy Fiber synapses in the hippocampus
Proceedings of the National Academy of Sciences, 1999Co-Authors: Kaspar E. Vogt, Roger A. NicollAbstract:Mossy Fiber synapses form the major excitatory input into the autoassociative network of pyramidal cells in the CA3 area of the hippocampus. Here we demonstrate that at the Mossy Fiber synapses, glutamate and γ-aminobutyric acid (GABA) act as autaptic and heterosynaptic presynaptic inhibitory transmitters through metabotropic glutamate receptors (mGluRs) and GABAB receptors, respectively. Both GABAB receptors and mGluRs are activated through spillover from adjacent synapses. We demonstrate that glutamate spillover caused by brief tetanic activation of Mossy Fiber terminals remains intact at physiological temperatures. The activation of GABAB receptors increased the threshold for Mossy Fiber long-term potentiation (LTP), whereas activation of mGluRs did not have such an effect. We speculate that this heterosynaptic depression provides the Mossy Fiber synapses with a mechanism to efficiently shape input patterns into CA3, increasing the sparseness of the Mossy Fiber signal and enhancing the capacity and performance of the CA3 associative network. The increase in LTP threshold through activation of presynaptic inhibitory receptors imparts a piesynoptic associative nature to Mossy Fiber LTP.
Thomas P Sutula - One of the best experts on this subject based on the ideXlab platform.
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Ultrastructural features of sprouted Mossy Fiber synapses in kindled and kainic acid-treated rats.
The Journal of Comparative Neurology, 2003Co-Authors: Jose E Cavazos, Peisu Zhang, Romena Qazi, Thomas P SutulaAbstract:The Mossy Fiber pathway in the dentate gyrus undergoes sprouting and synaptic reorganization in response to seizures. The types of new synapses, their location and number, and the identity of their postsynaptic targets determine the functional properties of the reorganized circuitry. The goal of this study was to characterize the types and proportions of sprouted Mossy Fiber synapses in kindled and kainic acid-treated rats. In normal rats, synapses labeled by Timm histochemistry or dynorphin immunohistochemistry were rarely observed in the supragranular region of the inner molecular layer when examined by electron microscopy. In epileptic rats, sprouted Mossy Fiber synaptic terminals were frequently observed. The ultrastructural analysis of the types of sprouted synapses revealed that 1) in the supragranular region, labeled synaptic profiles were more frequently axospinous than axodendritic, and many axospinous synapses were perforated; 2) sprouted Mossy Fiber synaptic terminals formed exclusively asymmetric, putatively excitatory synapses with dendritic spines and shafts in the supragranular region and with the soma of granule cells in the granule cell layer; 3) in contrast to the large sprouted Mossy Fiber synapses in resected human epileptic hippocampus, the synapses formed by sprouted Mossy Fibers in rats were smaller; and 4) in several cases, the postsynaptic targets of sprouted synapses were identified as granule cells, but, in one case, a sprouted synaptic terminal formed a synapse with an inhibitory interneuron. The results demonstrate that axospinous asymmetric synapses are the most common type of synapse formed by sprouted Mossy Fiber terminals, supporting the viewpoint that most sprouted Mossy Fibers contribute to recurrent excitation in epilepsy. J. Comp. Neurol. 458:272–292, 2003. © 2003 Wiley-Liss, Inc.
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activation of the dentate gyrus by pentylenetetrazol evoked seizures induces Mossy Fiber synaptic reorganization
Brain Research, 1992Co-Authors: Golijeh Golarai, Jose E Cavazos, Thomas P SutulaAbstract:Abstract Kindled seizures evoked by electrical stimulation of limbic pathways in the rat induce sprouting and synaptic reorganization of the Mossy Fiber pathway in the dentate gyrus (DG). To investigate whether seizures evoked by different methods also induce reorganization of this pathway, the distribution of Mossy Fiber terminals in the DG was examined with Timm histochemistry after systemic administration of pentylenetetrazol, a chemoconvulsant that reduces Cl− mediated GABAergic inhibition. Myoclonic seizures evoked by subconvulsant doses of pentylenetetrazol (24 mg/kg i.p.) were not accompanied by electrographic seizures in the DG, and did not induce Mossy Fiber sprouting. Generalized tonic-clonic seizures evoked by repeated administration of PTZ (24 mg/kg i.p.) were consistently accompanied by electrographic seizure activity in the DG, and induced sprouting and synaptic reorganization of the Mossy Fiber pathway. The results demonstrated that repeated generalized tonic-clonic seizures evoked by pentylenctetrazol induced Mossy Fiber synaptic reorganization when ictal electrographic discharges activated the circuitry of the DG.
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Mossy Fiber synaptic reorganization induced by kindling time course of development progression and permanence
The Journal of Neuroscience, 1991Co-Authors: Jose E Cavazos, Golijeh Golarai, Thomas P SutulaAbstract:Recent studies have revealed that Mossy Fiber axons of granule cells in the dentate gyrus undergo reorganization of their terminal projections in both animal models of epilepsy and human epilepsy. This synaptic reorganization has been demonstrated by the Timm method, a histochemical technique that selectively labels synaptic terminals of Mossy Fibers because of their high zinc content. It has been generally presumed that the reorganization of the terminal projections of the Mossy Fiber pathway is a consequence of axonal sprouting and synaptogenesis by Mossy Fibers. To evaluate this possibility further, the time course for development of Timm granules, which correspond ultrastructurally to Mossy Fiber synaptic terminals, was examined in the supragranular layer of the dentate gyrus at the initiation of kindling stimulation with an improved scoring method for assessment of alterations in Timm histochemistry. The progression and permanence of this histological alteration were similarly evaluated during the behavioral and electrographic evolution of kindling evoked by perforant path, amygdala, or olfactory bulb stimulation. Mossy Fiber synaptic terminals developed in the supragranular region of the dentate gyrus by 4 d after initiation of kindling stimulation in a time course compatible with axon sprouting. The induced alterations in the terminal projections of the Mossy Fiber pathway progressed with the evolution of behavioral kindled seizures, became permanent in parallel with the development of longlasting susceptibility to evoked seizures, and were observed as long as 8 months after the last evoked kindled seizure. The results demonstrated a strong correlation between Mossy Fiber synaptic reorganization and the development, progression, and permanence of the kindling phenomenon.
Jose E Cavazos - One of the best experts on this subject based on the ideXlab platform.
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Ultrastructural features of sprouted Mossy Fiber synapses in kindled and kainic acid-treated rats.
The Journal of Comparative Neurology, 2003Co-Authors: Jose E Cavazos, Peisu Zhang, Romena Qazi, Thomas P SutulaAbstract:The Mossy Fiber pathway in the dentate gyrus undergoes sprouting and synaptic reorganization in response to seizures. The types of new synapses, their location and number, and the identity of their postsynaptic targets determine the functional properties of the reorganized circuitry. The goal of this study was to characterize the types and proportions of sprouted Mossy Fiber synapses in kindled and kainic acid-treated rats. In normal rats, synapses labeled by Timm histochemistry or dynorphin immunohistochemistry were rarely observed in the supragranular region of the inner molecular layer when examined by electron microscopy. In epileptic rats, sprouted Mossy Fiber synaptic terminals were frequently observed. The ultrastructural analysis of the types of sprouted synapses revealed that 1) in the supragranular region, labeled synaptic profiles were more frequently axospinous than axodendritic, and many axospinous synapses were perforated; 2) sprouted Mossy Fiber synaptic terminals formed exclusively asymmetric, putatively excitatory synapses with dendritic spines and shafts in the supragranular region and with the soma of granule cells in the granule cell layer; 3) in contrast to the large sprouted Mossy Fiber synapses in resected human epileptic hippocampus, the synapses formed by sprouted Mossy Fibers in rats were smaller; and 4) in several cases, the postsynaptic targets of sprouted synapses were identified as granule cells, but, in one case, a sprouted synaptic terminal formed a synapse with an inhibitory interneuron. The results demonstrate that axospinous asymmetric synapses are the most common type of synapse formed by sprouted Mossy Fiber terminals, supporting the viewpoint that most sprouted Mossy Fibers contribute to recurrent excitation in epilepsy. J. Comp. Neurol. 458:272–292, 2003. © 2003 Wiley-Liss, Inc.
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activation of the dentate gyrus by pentylenetetrazol evoked seizures induces Mossy Fiber synaptic reorganization
Brain Research, 1992Co-Authors: Golijeh Golarai, Jose E Cavazos, Thomas P SutulaAbstract:Abstract Kindled seizures evoked by electrical stimulation of limbic pathways in the rat induce sprouting and synaptic reorganization of the Mossy Fiber pathway in the dentate gyrus (DG). To investigate whether seizures evoked by different methods also induce reorganization of this pathway, the distribution of Mossy Fiber terminals in the DG was examined with Timm histochemistry after systemic administration of pentylenetetrazol, a chemoconvulsant that reduces Cl− mediated GABAergic inhibition. Myoclonic seizures evoked by subconvulsant doses of pentylenetetrazol (24 mg/kg i.p.) were not accompanied by electrographic seizures in the DG, and did not induce Mossy Fiber sprouting. Generalized tonic-clonic seizures evoked by repeated administration of PTZ (24 mg/kg i.p.) were consistently accompanied by electrographic seizure activity in the DG, and induced sprouting and synaptic reorganization of the Mossy Fiber pathway. The results demonstrated that repeated generalized tonic-clonic seizures evoked by pentylenctetrazol induced Mossy Fiber synaptic reorganization when ictal electrographic discharges activated the circuitry of the DG.
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Mossy Fiber synaptic reorganization induced by kindling time course of development progression and permanence
The Journal of Neuroscience, 1991Co-Authors: Jose E Cavazos, Golijeh Golarai, Thomas P SutulaAbstract:Recent studies have revealed that Mossy Fiber axons of granule cells in the dentate gyrus undergo reorganization of their terminal projections in both animal models of epilepsy and human epilepsy. This synaptic reorganization has been demonstrated by the Timm method, a histochemical technique that selectively labels synaptic terminals of Mossy Fibers because of their high zinc content. It has been generally presumed that the reorganization of the terminal projections of the Mossy Fiber pathway is a consequence of axonal sprouting and synaptogenesis by Mossy Fibers. To evaluate this possibility further, the time course for development of Timm granules, which correspond ultrastructurally to Mossy Fiber synaptic terminals, was examined in the supragranular layer of the dentate gyrus at the initiation of kindling stimulation with an improved scoring method for assessment of alterations in Timm histochemistry. The progression and permanence of this histological alteration were similarly evaluated during the behavioral and electrographic evolution of kindling evoked by perforant path, amygdala, or olfactory bulb stimulation. Mossy Fiber synaptic terminals developed in the supragranular region of the dentate gyrus by 4 d after initiation of kindling stimulation in a time course compatible with axon sprouting. The induced alterations in the terminal projections of the Mossy Fiber pathway progressed with the evolution of behavioral kindled seizures, became permanent in parallel with the development of longlasting susceptibility to evoked seizures, and were observed as long as 8 months after the last evoked kindled seizure. The results demonstrated a strong correlation between Mossy Fiber synaptic reorganization and the development, progression, and permanence of the kindling phenomenon.
Atsushi Takeda - One of the best experts on this subject based on the ideXlab platform.
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Zinc-mediated attenuation of hippocampal Mossy Fiber long-term potentiation induced by forskolin.
Neurochemistry International, 2010Co-Authors: Masaki Ando, Naoto Oku, Atsushi TakedaAbstract:The rise in presynaptic calcium induced by high-frequency stimulation activates the calcium-calmodulin-sensitive adenylyl cyclase (AC) 1 followed by the induction of long-term potentiation (LTP) at the hippocampal Mossy Fiber-CA3 synapse. Zinc is released with glutamate from Mossy Fiber terminals. However, the role of the zinc in Mossy Fiber LTP is controversial. In the present study, the mechanism of zinc-mediated attenuation of Mossy Fiber LTP was examined in that induced by forskolin, an AC activator. Mossy Fiber LTP induced by tetanic stimulation (100 Hz for 1 s) was attenuated in the presence of 5 microM ZnCl(2), whereas that induced by forskolin under test stimulation (0.1 Hz) was not attenuated. Forskolin-induced Mossy Fiber LTP was attenuated by perfusion with 100 microM ZnCl(2) prior to the induction. However, the zinc (100 microM) pre-perfusion did not attenuate Mossy Fiber LTP induced by Sp-cAMPS, an activator of protein kinase A, under test stimulation. Zinc is necessary to be taken up into Mossy Fiber boutons for effectively inhibiting AC activity. In hippocampal slices labeled with ZnAF-2 DA, a membrane-permeable zinc indicator, intracellular ZnAF-2 signal was increased during tetanic stimulation in the presence of 5 microM ZnCl(2), but not under test stimulation. Intracellular ZnAF-2 signal was increased under test stimulation in the presence of 100 microM ZnCl(2). These results suggest that zinc taken up into Mossy Fibers attenuates forskolin-induced Mossy Fiber LTP via inhibition of AC activity. The significance of endogenous zinc uptake by Mossy Fibers is discussed focused on tetanus-induced Mossy Fiber LTP.
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attenuation of hippocampal Mossy Fiber long term potentiation by low micromolar concentrations of zinc
Journal of Neuroscience Research, 2008Co-Authors: Atsushi Takeda, Shingo Kanno, Naomi Sakurada, Masaki AndoAbstract:The role of zinc in long-term potentiation (LTP) at hippocampal Mossy Fiber synapses is controversial because of the contrary results obtained when using zinc chelators. On the basis of the postulation that exogenous zinc enhances the action of zinc released from Mossy Fibers, Mossy Fiber LTP after tetanic stimulation (100 Hz, 1 sec) was checked in the presence of exogenous zinc at low micromolar concentrations. Mossy Fiber LTP was significantly attenuated in the presence of 5–30 μM ZnCl2, and the amplitude of field excitatory postsynaptic potentials 60 min after tetanic stimulation was decreased to almost the basal level. Mossy Fiber LTP was also attenuated in the presence of 5 μM ZnCl2 5 min after tetanic stimulation. The present study is the first to demonstrate that low micromolar concentrations of zinc attenuate Mossy Fiber LTP. When Mossy Fiber LTP was induced in the presence of CaEDTA and ZnAF-2 DA, a membrane-impermeable and a membrane-permeable zinc chelator, respectively, extracellular and intracellular chelation of zinc enhanced a transient posttetanic potentiation (PTP) without altering LTP. It is likely that zinc released by tetanic stimulation is immediately taken up into the Mossy Fibers and attenuates Mossy Fiber PTP. These results suggest that attenuation of PTP rather than LTP at Mossy Fiber synapses is a more physiological role for endogenous zinc. Targeting molecules of zinc in Mossy Fiber LTP seem to be different between during and after LTP induction because of the differential synaptic activity between them. © 2008 Wiley-Liss, Inc.
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inhibition of presynaptic activity by zinc released from Mossy Fiber terminals during tetanic stimulation
Journal of Neuroscience Research, 2006Co-Authors: Akira Minami, Naomi Sakurada, Sayuri Fuke, Kazuya Kikuchi, Tetsuo Nagano, Atsushi TakedaAbstract:Zinc exists in high densities in the giant boutons of hippocampal Mossy Fibers. On the basis of the evidence that zinc decreases extracellular glutamate concentration in the hippocampus, the presynaptic action of zinc released from Mossy Fibers during high-frequency (tetanic) stimulation was examined using hippocampal slices. The increase in zinc-specific fluorescent signals was observed in both extracellular and intracellular compartments in the Mossy Fiber terminals during the delivery of tetanic stimuli (100 Hz, 1 sec) to the dentate granule cell layer, suggesting that zinc released from Mossy Fibers is immediately retaken up by Mossy Fibers. When Mossy Fiber terminals were preferentially double-stained with zinc and calcium indicators and tetanic stimuli (100 Hz, 1 sec) were delivered to the dentate granule cell layer, the increase in calcium orange signal during the stimulation was enhanced in Mossy Fiber terminals by addition of CaEDTA, a membrane-impermeable zinc chelator, and was suppressed by addition of zinc. The decrease in FM4-64 signal (vesicular exocytosis) during tetanic stimulation (10 Hz, 180 sec), which induced Mossy Fiber long-term potentiation, was also enhanced in Mossy Fiber terminals by addition of CaEDTA and was suppressed by addition of zinc. The present study demonstrates that zinc released from Mossy Fibers may be a negative-feedback factor against presynaptic activity during tetanic stimulation.
John M. Sarvey - One of the best experts on this subject based on the ideXlab platform.
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Induction of Mossy Fiber→CA3 Long-Term Potentiation Requires Translocation of Synaptically Released Zn2+
The Journal of Neuroscience, 2001Co-Authors: Yang V. Li, Christopher J. Hough, Christopher J. Frederickson, John M. SarveyAbstract:The mammalian CNS contains an abundance of chelatable Zn2+ sequestered in the vesicles of glutamatergic terminals. These vesicles are particularly numerous in hippocampal Mossy Fiber synapses of the hilar and CA3 regions. Our recent observation of frequency-dependent Zn2+ release from Mossy Fiber synaptic terminals and subsequent entry into postsynaptic neurons has prompted us to investigate the role of synaptically released Zn2+ in the induction of long-term potentiation (LTP) in field CA3 of the hippocampus. The rapid removal of synaptically released Zn2+ with the membrane-impermeable Zn2+ chelator CaEDTA (10 mm) blocked induction of NMDA receptor-independent Mossy Fiber LTP by high-frequency electrical stimulation (HFS) in rat hippocampal slices. Mimicking Zn2+ release by bath application of Zn2+ (50–100 μm) without HFS induced a long-lasting potentiation of synaptic transmission that lasted more than 3 hr. Moreover, our experiments indicate the effects of Zn2+ were not attributable to its interaction with extracellular membrane proteins but required its entry into presynaptic or postsynaptic neurons. Co-released glutamate is also essential for induction of LTP under physiological conditions, in part because it allows Zn2+ entry into postsynaptic neurons. These results indicate that synaptically released Zn2+, acting as a second messenger, is necessary for the induction of LTP at Mossy Fiber→CA3 synapses of hippocampus.
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induction of Mossy Fiber ca3 long term potentiation requires translocation of synaptically released zn2
The Journal of Neuroscience, 2001Co-Authors: Christopher J. Hough, Christopher J. Frederickson, John M. SarveyAbstract:The mammalian CNS contains an abundance of chelatable Zn2+ sequestered in the vesicles of glutamatergic terminals. These vesicles are particularly numerous in hippocampal Mossy Fiber synapses of the hilar and CA3 regions. Our recent observation of frequency-dependent Zn2+ release from Mossy Fiber synaptic terminals and subsequent entry into postsynaptic neurons has prompted us to investigate the role of synaptically released Zn2+ in the induction of long-term potentiation (LTP) in field CA3 of the hippocampus. The rapid removal of synaptically released Zn2+ with the membrane-impermeable Zn2+ chelator CaEDTA (10 mm) blocked induction of NMDA receptor-independent Mossy Fiber LTP by high-frequency electrical stimulation (HFS) in rat hippocampal slices. Mimicking Zn2+ release by bath application of Zn2+ (50–100 μm) without HFS induced a long-lasting potentiation of synaptic transmission that lasted more than 3 hr. Moreover, our experiments indicate the effects of Zn2+ were not attributable to its interaction with extracellular membrane proteins but required its entry into presynaptic or postsynaptic neurons. Co-released glutamate is also essential for induction of LTP under physiological conditions, in part because it allows Zn2+ entry into postsynaptic neurons. These results indicate that synaptically released Zn2+, acting as a second messenger, is necessary for the induction of LTP at Mossy Fiber→CA3 synapses of hippocampus.
