| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
REPORT
1Departments of Neuroscience and 2Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas; and 3Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan
Submitted 14 June 2007; accepted in final form 5 January 2008
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
). High-frequency stimulation (HFS) of Schaffer collaterals effectively induces LTP in area CA1 of the hippocampus by activating calcium-permeable N-methyl-D-aspartate (NMDA) receptors (Malenka and Nicoll 1999), resulting in a rise in postsynaptic calcium that is necessary for LTP induction (Lynch et al. 1983; Malenka et al. 1988). Activation of NMDA receptors in hippocampal slices results in the production of superoxide, which can stimulate the phosphorylation of extracellular signal-regulated kinase (ERK) (Bindokas et al. 1996; Kanterewicz et al. 1998). Both superoxide and ERK are required for NMDA receptor-dependent LTP (English and Sweatt 1997; Klann 1998). Furthermore, treatment of hippocampal slices with superoxide generated from xanthine/xanthine oxidase (X/XO) induces a long-lasting potentiation of synaptic transmission that occludes HFS-induced LTP, suggesting that activation of similar signaling pathways occurs during both types of potentiation (Knapp and Klann 2002). However, NMDA receptor activation is not necessary for induction of superoxide-induced potentiation, indicating that superoxide likely acts downstream of the NMDA receptor (Knapp and Klann 2002). Because increases in postsynaptic intracellular calcium are typically required for long-term changes in synaptic efficiency, we hypothesized that there are other sources of calcium that mediate superoxide-induced potentiation.
Ryanodine receptors (RyRs) mediate calcium-induced calcium release (CICR) from intracellular stores. They are extremely sensitive to redox modifications and have been shown to modulate hippocampal LTP (reviewed in Hidalgo 2005). Nanomolar concentrations of ryanodine that activate the channel enhance LTP; in contrast, inhibitory micromolar concentrations reduce LTP (Lu and Hawkins 2002). In addition, hydrogen peroxide (H2O2) stimulates the phosphorylation of ERK in hippocampal slices through an oxidative modification of RyRs (Kemmerling et al. 2007). All three RyR isoforms are expressed in area CA1 of the hippocampus in adult mice, but the RyR3 subtype is significantly enriched in this region (Mori et al. 2000). Previous studies on RyR3 knockout (KO) mice have established a role for this subtype in hippocampal synaptic plasticity and hippocampus-dependent learning tasks (Balschun et al. 1999; Kouzu et al. 2000; Shimuta et al. 2001). RyR3 KO mice display significantly reduced LTP following various stimulation protocols (Balschun et al. 1999; Shimuta et al. 2001). Redox regulation of RyR3 receptors may partially mediate these effects as single-channel recordings indicate that oxidizing reagents activate the channel, whereas reducing reagents inhibit it (Murayama et al. 1999). Thus it is possible that RyRs, most notably RyR3, modulate the magnitude of LTP via activation of ERK.
Calcium influx through L-type voltage-gated calcium channels may also be necessary for superoxide-induced potentiation. A low concentration of H2O2 (1 µM), a molecule that partially mediates superoxide-induced potentiation (Knapp and Klann 2002), increased the magnitude of LTP (Kamsler and Segal 2003). This effect was dependent on activation of L-type calcium channels but not NMDA receptors (Kamsler and Segal 2003). Furthermore, a functional coupling between RyRs and L-type calcium channels has been established in the dentate gyrus and cerebellar granule cells (Chavis et al. 1996; Welsby et al. 2006). Thus L-type channels may be an important calcium source upstream of RyRs that are required for the redox component of LTP.
Herein, we determined whether superoxide treatment enhanced activation of RyRs and whether RyR3 specifically was necessary for the expression of superoxide-induced potentiation in hippocampal area CA1. We found that superoxide-induced LTP was abolished in RyR3 KO mice, indicating that redox modification of this enriched subtype of RyRs is a source of calcium necessary for potentiation of synaptic transmission induced by superoxide. L-type calcium channels also were required, indicating a functional coupling of these channels with RyR3 during superoxide-induced potentiation. Moreover, increased phosphorylation of ERK following the application of superoxide to slices was mediated by RyR3 and activation of ERK was necessary for superoxide-induced LTP. These findings demonstrate that several components of signaling pathways known to modulate tetanus-induced LTP are critical for expression of superoxide-induced LTP.
|
METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
XO, ryanodine, nifedipine, and U0124 were purchased from Calbiochem (La Jolla, CA). X was purchased from Sigma (St. Louis, MO). Rabbit anti-dually phosphorylated ERK (pp-ERK) and rabbit anti-total ERK (ERK) were purchased from Promega (Madison, WI). Mouse anti-RyR was purchased from Affinity Bioreagents (Golden, CO).
Mice
Generation of the RyR3 KO mice is described elsewhere (Takeshima et al. 1996). The RyR3 KO mice were bred on a C57Bl6 genetic background.
Preparation of hippocampal slices and extracellular recordings
Hippocampi from adult (3–6 mo) male C57Bl/6 mice were removed, and 400 µm slices were prepared with a McIlwain tissue chopper. The slices were perfused for 1–2 h with artificial cerebrospinal fluid (ACSF) (containing, in mM: 125 NaCl, 2.5 KCl, 1.25 NaH2PO4, 2 CaCl2, 1 MgCl2, 25 NaHCO3, and 25 D-glucose continuously bubbled with a 95% O2-5% CO2) in an interface chamber at 30°C. A bipolar stimulating electrode was placed to stimulate the Schaffer collaterals emanating from CA3 pyramidal neurons, and the recording electrode was placed in the stratum radiatum in area CA1. Stimuli were given at a current that elicited 50% of the maximum initial slope of the extracellular field excitatory postsynaptic potential (fEPSP) every 20 s and responses were averaged over a 2-min interval.
Pharmacology
Baseline responses were recorded for 20 min before application of any drugs. All slices were treated with 20 µg/ml X and 17 µg/ml XO for 10 min. For some experiments, slices were treated with 10 µM ryanodine for 30 min before and during X/XO application. In another set of experiments, slices were treated with either the MEK inhibitor U0126 (20 µM) or U0124 (an inactive analogue of U0126) 60 min before and during the X/XO application. Responses were monitored 60 min after washout of all reagents.
Tritiated ([3H]) ryanodine binding
Hippocampal slices were prepared as described in the preceding text and allowed to recover for 2 h in 15 ml ACSF at 30°C. The slices (7/vial) were incubated for 10 min with 20 µg/ml X and 17 µg/ml XO (or boiled XO) and immediately snap-frozen on dry ice. The slices then were homogenized in high sucrose buffer (320 mM sucrose, 5 mM HEPES, and 10 µl/ml protease and phosphatase inhibitors), and microsomes were extracted by differential centrifugation. The pellet containing the microsome extract was resuspended in 150 mM NaCl, 50 mM Tris pH 7.5, 0.1% CHAPS, and 10 µl/ml protease and phosphatase inhibitors, and total protein concentrations were determined. Hippocampal slices from 10 mice were used for seven replicates of the drug treatment. Microsome extracts from all seven replicates were pooled to provide 300 µg of protein for two binding assays, requiring 150 µg of protein per assay. The 150 µg of protein was divided into five tubes containing 30 µg per tube of which three were used to measure specific activity and the other two for nonspecific activity. Microsome extracts were incubated in 300 mM NaCl, 100 µM CaCl2, 0.1 mg/ml BSA, 0.1% CHAPS, 50 mM MOPS pH 7.4, and 10 nM [3H] ryanodine to measure specific activity. To measure nonspecific activity, 10 µM cold ryanodine was added to the buffer. Samples were incubated 14–16 h, and the unbound tritium was washed through a filter with buffer. The activity left on the filter was measured by a scintillation counter.
Western blot analysis
Hippocampal slices were prepared as described in the preceding text and allowed to recover for 2 h in 15 ml ACSF at 30°C. The slices (3/vial) were incubated for 10 min with 20 µg/ml X and 17 µg/ml XO (or boiled XO) and snap frozen on dry ice 5 min after treatment. The slices then were homogenized in high sucrose buffer (320 mM sucrose, 5 mM HEPES, and 10 µl/ml protease and phosphatase inhibitors), and total protein concentrations were determined. Ten micrograms of protein were loaded on a 12% SDS-PAGE gel and resolved by electrophoresis. Separated proteins were transferred from the SDS-PAGE gel to Immobilon-P membranes (Millipore, Bedford, MA) using a transfer tank. Following transfer the membranes were incubated in blocking solution containing 0.2% I-block, 50 mM Tris-HCl pH 7.5, 150 mM NaCl, and 0.1% Tween-20 at room temperature (RT) for 1 h. The blots then were incubated for 1 h at RT with primary antibodies (Ab) against pp-ERK diluted 1:3000 in blocking solution. The blots were washed three times for 15 min in Tris-buffered saline (50 mM Tris-HCl pH 7.5, 150 mM NaCl, and 0.05% Tween-20), then incubated at RT for 1 h with secondary (horseradish peroxidase-conjugated anti-rabbit) Ab diluted 1:10,000 in blocking solution. The blots were washed again and exposed to Kodak film using ECL chemiluminescence. Normalization of pp-ERK to total ERK for all experiments was achieved by stripping and probing the blots for total ERK following the protocol described above. For RyR blots, 20 µg of protein from microsome extracts were loaded into a 5% SDS-PAGE gel. Blots were incubated with anti-RyR Ab for 2.5 h at RT diluted 1:2,000 in blocking solution. The remainder of the protocol was performed as described above.
Data analysis
The results for all experiments are presented as means ± SE. For comparisons between two groups, a two-tailed Student's t-test was used. Comparisons between multiple groups were analyzed using a one-way ANOVA followed by a Newman-Keuls multiple comparisons test. Error probabilities with P values <0.05 were considered statistically significant.
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
The unique redox sensitivity of RyRs prompted us to investigate whether a brief exposure to superoxide treatment would enhance their activation in the hippocampus. The degree of activation of RyRs isolated from hippocampal slices immediately following 10 min of X/XO treatment was assessed with a [3H] ryanodine-binding assay, and their presence in the microsome extract was confirmed with Western blot analysis. We observed two bands that likely represent the three RyR subtypes in the hippocampus (Fig. 1A, inset). A similar "doublet" representing RyR3 and RyR1/RyR2 was observed previously (Jeyakumar et al. 1998). Binding of [3H]ryanodine was enhanced in microsome extracts from hippocampal slices treated with X/XO ([3H] ryanodine = 139.8 ± 6% of control, n = 2; each in triplicate Fig. 1A) compared with those treated with X/boiled XO ([3H] ryanodine = 100 ± 4% of control, n = 2; each in triplicate). These data are consistent with the possibility that hippocampal RyRs are activated by superoxide treatment.
|
In light of the ability of superoxide to modulate RyR activity, we hypothesized that RyR-mediated CICR from intracellular stores is a calcium source mediating superoxide-induced potentiation. Treatment of hippocampal slices for 10 min with X/XO induced a transient depression followed by a significant long-lasting potentiation of synaptic transmission (fEPSP slope = 116 ± 0.4% of baseline, n = 7; Fig. 1B). The superoxide-induced potentiation was blocked, and the recovery from depression prolonged when the hippocampal slices were treated with a concentration of ryanodine that inhibits function of all RyRs (10 µM) for half an hour before and during addition of X/XO (fEPSP slope = 95 ± 0.6% of baseline, n = 8; Fig. 1, B and E). These results are consistent with the hypothesis that CICR through RyRs mediates superoxide-induced potentiation.
We also examined superoxide-induced potentiation in RyR3 KO mice. Although the recovery from depression was the same in RyR3 KO and WT mice, there was a significant suppression of potentiation in the RyR3 KO mice (fEPSP slope = 99 ± 0.8% of baseline, n = 6; Fig. 1, C and E). When the other RyR subtypes were pharmacologically blocked in hippocampal slices from the RyR3 KO mice, the results were indistinguishable from those obtained from WT slices exposed to the same pharmacological conditions except for a significant (P < 0.001, paired t-test) change in baseline synaptic transmission following the addition of 10 µM ryanodine (fEPSP slope = 106 ± 0.24% of baseline for WT and 95 ± 0.51% of baseline for RyR3 KO). These changes in baseline synaptic transmission may be a result of this concentration of ryanodine (10 µM) causing a long-lasting subconductance state rather than fully inhibiting activity of the receptor (Murayama et al. 1999). Taken together, these data indicate that expression of superoxide-induced potentiation is mediated by RyR3 activation.
RyR3 is required for superoxide-induced activation of ERK
Phosphorylation of ERK is stimulated in hippocampal slices following superoxide treatment (Kanterewicz et al. 1998). We hypothesized that RyR activation, specifically RyR3, is responsible for this effect. Consistent with previous findings, we found that superoxide significantly enhanced the phosphorylation of ERK2 (129 ± 10.7% of control, n = 7; Fig. 2A). Phosphorylation of ERK2 was not altered by superoxide in hippocampal slices pretreated with 10 µM ryanodine (94 ± 11.4% of control, n = 6; Fig. 2A) or in those from RyR3 KO mice (91 ± 3.2% of control, n = 4; Fig. 2B). Thus our findings indicate that superoxide-induced activation of ERK is RyR3 dependent.
|
Considering the aforementioned superoxide-induced activation of ERK, we postulated that this event is a component of the signaling cascades that mediate superoxide-induced potentiation. Blockade of ERK activation achieved by 1-h incubation with the MEK inhibitor U0126 before and during X/XO treatment enhanced the transient depression and eliminated the potentiation (fEPSP slope = 100 ± 0.6% of baseline, n = 10; Fig. 2, C and D). Superoxide-induced potentiation was observed in hippocampal slices treated in the same manner with U0124, the inactive analogue of the MEK inhibitor (fEPSP slope = 111 ± 1.0% of baseline, n = 8; Fig. 2, C and D). These results strongly suggest that superoxide is a messenger molecule that induces potentiation through similar pathways activated during HFS-induced LTP.
Superoxide-induced potentiation is dependent on L-type calcium channel activation
Calcium flux through ryanodine receptors is induced in the presence of calcium, making it a calcium amplification system. This suggests the presence of an additional calcium source upstream of RyR3 that is necessary for superoxide-induced potentiation. We investigated the contribution of L-type calcium channels because they have been shown to be a component of signaling cascades involving RyRs in both the dentate gyrus and cerebellum (Chavis et al. 1996; Welsby et al. 2006). Application of the L-type calcium channel blocker nifedipine (10 µM) for half an hour before and during addition of X/XO blocked superoxide-induced potentiation (fEPSP slope = 97 ± 1.0% of baseline, n = 6; Fig. 3). These results indicate that a functional coupling between RyR3 and L-type calcium channels are involved in superoxide-induced potentiation.
|
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
Superoxide previously has been established as a signaling molecule required for LTP induction, but its targets have remained elusive (Kishida and Klann 2007; Klann 1998; Thiels et al. 2000). Superoxide-induced potentiation and HFS-induced LTP occlude one another, suggesting that they share similar signaling pathways (Knapp and Klann 2002). Thus superoxide-induced potentiation is a viable paradigm that could be used to elucidate the targets of superoxide during LTP induction. The effectiveness of this paradigm for determining targets of superoxide during LTP induction is illustrated in studies focusing on protein kinase C (PKC). Persistent activation of PKC is necessary for LTP induction and maintenance (Klann et al. 1993; Wang and Feng 1992). The increase in cofactor-dependent PKC activity in area CA1 of hippocampal slices observed following HFS was abrogated by the superoxide-specific scavenger superoxide dismutase (SOD) (Klann et al. 1998). Potentiation induced by superoxide is also dependent on persistent PKC activation (Knapp and Klann 2002). The results of our present study have identified two more components, RyR3 and ERK, of the signaling cascade necessary for superoxide-induced potentiation that are also important for LTP.
There are many potential neuronal sources of superoxide including mitochondria, monoamine oxidase, cyclooxygenase, nitric oxide synthase, and NADPH oxidase (Kishida and Klann 2007). The only one of the aforementioned sources directly linked to synaptic plasticity and learning and memory is NADPH oxidase. Pharmacological inhibitors of NADPH oxidase blocked LTP and NMDA receptor-dependent activation of ERK in area CA1 of the hippocampus (Kishida et al. 2005, 2006). LTP also was abolished in mice lacking either one of two subunits, gp91phox or p47phox, critical for NADPH oxidase-dependent superoxide production (Kishida et al. 2006). These mice display mild deficits in hippocampus-dependent memory tasks as well (Kishida et al. 2006). Thus NADPH oxidase is likely one of the sources of superoxide required for LTP and memory function.
Although X/XO is a superoxide-generating system, it is not our intention to suggest that superoxide is the only reactive oxygen species (ROS) involved in inducing superoxide-induced potentiation. SOD is a scavenger of superoxide that catalyzes the conversion of superoxide to hydrogen peroxide (H2O2), which can react with iron ions to form hydroxyl radicals (OH·) (Kamsler and Segal 2004). Catalase, an enzyme that converts H2O2 to water and oxygen molecules, was shown to attenuate superoxide-induced potentiation and completely block the transient depression in synaptic transmission observed during X/XO treatment in hippocampal slices from rats (Knapp and Klann 2002). A low concentration of H2O2 (1 µM) was shown to stimulate ERK and cAMP-responsive element-binding protein (CREB) phosphorylation, both of which are critical for LTP and memory function (reviewed in Silva 2003), in hippocampal slices that was dependent on activation of RyRs (Kemmerling et al. 2007). Inhibition of ERK phosphorylation triggered by H2O2 by the MEK inhibitor U0126 may be responsible for the enhancement of the transient depression observed (Fig. 2C). Furthermore, in cultured hippocampal neurons H2O2-induced phosphorylation of ERK and CREB was accompanied by increased S-glutathionylation, a type of oxidative modification, of RyRs (Kemmerling et al. 2007). Thus oxidative modifications of RyRs are likely responsible for the increase in RyR activation observed following superoxide treatment (Hidalgo 2005).
Our results also suggest the possibility of a role for OH· in superoxide-induced potentiation. Potentiation was attenuated slightly in hippocampal slices treated with X/XO and the inactive analogue of the MEK inhibitor, U0124, compared with those only treated with X/XO. We suspect that this may have occurred because the U0124 is dissolved in dimethylsulfoxide (DMSO), which acts as a scavenger of OH·. In support of this idea is the finding that treatment of PC12 cells with iron, which accelerates the conversion of H2O2 to OH·, enhances phosphorylation of ERK and induces calcium transients that were blocked by ryanodine (Munoz et al. 2006). Our results are in agreement with current literature suggesting that multiple ROS can regulate RyRs and are important modulators of synaptic plasticity.
There is evidence for the involvement of both pre- and postsynaptic changes in superoxide-induced potentiation. Analysis of paired pulse facilitation (PPF) showed an increase in PPF immediately after washout of X/XO, which corresponds to the transient depression observed (Knapp and Klann 2002). A decrease in PPF also was observed 20 and 30 min after washout of X/XO but not at any later time points (Knapp and Klann 2002). These findings suggest the possibility of a presynaptic locus for these phases of plasticity. The effects of ryanodine on baseline synaptic transmission also may be mediated presynaptically. Ryanodine (2 µM) increases the probability of successful transmission when there is a low probability (P ranging from 0.03 to 0.32) of release at CA3–CA1 synapses, and these changes are accompanied by a decreased PPR (the ratio of the mean amplitude of all events including failures after the second stimulation over the mean amplitude of all events including failures after the first stimulation) and coefficient of variation (Magueresse and Cherubini 2007). RyRs are present both pre- and postsynaptically and superoxide in the extracellular space has been demonstrated to be important for LTP induction (Klann et al. 1998), so it is reasonable to consider that both pre- and postsynaptic components of the synapse are important for superoxide-induced potentiation.
In conclusion, our studies are the first to show that redox modulation of RyRs is able to induce plasticity in area CA1 of the hippocampus. Our data also reveal two more components of the redox signaling module, RyR3 and ERK, that mediate both superoxide-induced potentiation and HFS-induced LTP (English and Sweatt 1997; Shimuta et al. 2001). These results are consistent with the idea that superoxide produced in area CA1 following HFS is important for the induction of LTP via the oxidative modification of RyRs. This question remains to be addressed in future studies.
|
GRANTS |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
|
ACKNOWLEDGMENTS |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
|
FOOTNOTES |
|---|
Address for reprint requests and other correspondence: E. Klann, Center for Neural Science, New York University, 4 Washington Place, Room 809, New York, NY 10003 (E-mail: eklann{at}cns.nyu.edu)
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
Bindokas VP, Jordan J, Lee CC, Miller RJ. Superoxide production in rat hippocampal neurons: selective imaging with hydroethidine. J Neurosci 16: 1324–1336, 1996.
Bliss TVP, Collingridge GL. A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361: 31–39, 1993.[CrossRef][Medline]
Chavis P, Fagni L, Lansman JB, Bockaert J. Functional coupling between ryanodine receptors and L-type calcium channels in neurons. Nature 382: 719–722, 1996.[CrossRef][Medline]
English JD, Sweatt JD. A requirement for the mitogen-activated protein kinase cascade in hippocampal long term potentiation. J Biol Chem 272: 19103–19106, 1997.
Hidalgo C. Cross talk between calcium and redox signalling cascades in muscle and neurons through the combined activation of ryanodine receptors/calcium release channels. Phil Trans R Soc B Biol Sci 360: 2237–2246, 2005.
Hidalgo C, Sanchez G, Barrientos G, Aracena-Parks P. A transverse tubule NADPH oxidase activity stimulates calcium release from isolated triads via ryanodine receptor type 1 S-glutathionylation. J Biol Chem 281: 26473–26482, 2006.
Jeyakumar LH, Copello JA, O'Malley AM, Wu G, Grassucci R, Wagenknecht T, Fleischer S. Purification and characterization of ryanodine receptor 3 from mammalian tissue. J Biol Chem 273: 16011–16020, 1998.
Kamsler A, Segal M. Hydrogen peroxide modulation of synaptic plasticity. J Neurosci 23: 269–276, 2003.
Kamsler A, Segal M. Hydrogen peroxide as a diffusible signal molecule in synaptic plasticity. Mol Neurobiol 29: 167–178, 2004.[CrossRef][Web of Science][Medline]
Kanterewicz BI, Knapp LT, Klann E. Stimulation of p42 and p44 mitogen-activated protein kinases by reactive oxygen species and nitric oxide in hippocampus. J Neurochem 70: 1009–1016, 1998.[Web of Science][Medline]
Kawakami M, Okabe E. Superoxide anion radical-triggered calcium release from cardiac sarcoplasmic reticulum through ryanodine receptor calcium channel. Mol Pharmacol 53: 497–503, 1998.
Kemmerling U, Munoz P, Muller M, Sanchez G, Aylwin ML, Klann E, Carrasco MA, Hidalgo C. Calcium release by ryanodine receptors mediates hydrogen peroxide-induced activation of ERK and CREB phosphorylation in N2a cells and hippocampal neurons. Cell Calcium 41: 491–502, 2007.[CrossRef][Web of Science][Medline]
Kishida KT, Hoeffer CA, Hu D, Pao M, Holland SM, Klann E. Synaptic plasticity deficits and mild memory impairments in mouse models of chronic granulomatous disease. Mol Cell Biol 26: 5908–5920, 2006.
Kishida KT, Klann E. Sources and targets of reactive oxygen species in synaptic plasticity and memory. Antioxid Redox Signal 9: 1–12, 2007.[CrossRef][Web of Science][Medline]
Kishida KT, Pao M, Holland SM, Klann E. NADPH oxidase is required for NMDA receptor-dependent activation of ERK in hippocampal area CA1. J Neurochem 94: 299–306, 2005.[CrossRef][Web of Science][Medline]
Klann E. Cell-permeable scavengers of superoxide prevent long-term potentiation in hippocampal area CA1. J Neurophysiol 80: 452–457, 1998.
Klann E, Chen S, Sweatt JD. Mechanism of protein kinase C activation during the induction and maintenance of long-term potentiation probed using a selective peptide substrate. Proc Natl Acad Sci USA 90: 8337–8341, 1993.
Klann E, Roberson ED, Knapp LT, Sweatt JD. A role for superoxide in protein kinase C activation and induction of long-term potentiation. J Biol Chem 273: 4516–4522, 1998.
Knapp LT, Klann E. Potentiation of hippocampal synaptic transmission by superoxide requires the oxidative activation of protein kinase C. J Neurosci 22: 674–683, 2002.
Kouzu Y, Moriya T, Takeshima H, Yoshioka T, Shibata S. Mutant mice lacking ryanodine receptor type 3 exhibit deficits of contextual fear conditioning and activation of calcium/calmodulin-dependent protein kinase II in the hippocampus. Brain Res Mol Brain Res 76: 142–150, 2000.[Medline]
Lu Y, Hawkins RD. Ryanodine receptors contribute to cGMP-induced late-phase LTP and CREB phosphorylation in the hippocampus. J Neurophysiol 88: 1270–1278, 2002.
Lynch G, Larson J, Kelso S, Barrionuevo G, Schottler F. Intracellular injections of EGTA block induction of hippocampal long-term potentiation. Nature 305: 719–721, 1983.[CrossRef][Medline]
Magueresse CL, Cherubini E. Presynaptic calcium stores contribute to nicotine-elicited potentiation of evoked synaptic transmission at CA3-CA1 connections in the neonatal rat hippocampus. Hippocampus 17: 316–325, 2007.[CrossRef][Web of Science][Medline]
Malenka RC, Kauer JA, Zucker RS, Nicoll RA. Postsynaptic calcium is sufficient for potentiation of hippocampal synaptic transmission. Science 242: 81–84, 1988.
Malenka RC, Nicoll RA. Long-term potentiation—a decade of progress? Science 285: 1870–1874, 1999.
Mori F, Fukaya M, Abe H, Wakabayashi K, Watanabe M. Developmental changes in expression of the three ryanodine receptor mRNAs in the mouse brain. Neurosci Lett 285: 57–60, 2000.[CrossRef][Web of Science][Medline]
Munoz P, Zavala G, Castillo K, Aguirre P, Hidalgo C, Nunez MT. Effect of iron on the activation of the MAPK/ERK pathway in PC12 neuroblastoma cells. Biol Res 39: 189–190, 2006.[Web of Science][Medline]
Murayama T, Oba T, Katayama E, Oyamada H, Oguchi K, Kobayashi M, Otsuka K, Ogawa Y. Further characterization of the type 3 ryanodine receptor (RyR3) purified from rabbit diaphragm. J Biol Chem 274: 17297–17308, 1999.
Shimuta M, Yoshikawa M, Fukaya M, Watanabe M, Takeshima H, Manabe T. Postsynaptic modulation of AMPA receptor-mediated synaptic responses and LTP by the type 3 ryanodine receptor. Mol Cell Neurosci 17: 921–930, 2001.[CrossRef][Web of Science][Medline]
Silva AJ. Molecular and cellular cognitive studies of the role of synaptic plasticity in memory. J Neurobiol 54: 224–237, 2003.[CrossRef][Web of Science][Medline]
Takeshima H, Ikemoto T, Nishi M, Nishiyama N, Shimuta M, Sugitani Y, Kuno J, Saito I, Saito H, Endo M, Iino M, Noda T. Generation and characterization of mutant mice lacking ryanodine receptor type 3. J Biol Chem 271: 19649–19652, 1996.
Thiels E, Urban NN, Gonzalez-Burgos GR, Kanterewicz BI, Barrionuevo G, Chu CT, Oury TD, Klann E. Impairment of long-term potentiation and associative memory in mice that overexpress extracellular superoxide dismutase. J Neurosci 20: 7631–7639, 2000.
Wang J, Feng D. Postsynaptic protein kinase C essential to induction and maintenance of long-term potentiation in the hippocampal CA1 region. Proc Natl Acad Sci USA 89: 2576–2580, 1992.
Welsby P, Rowan M, Anwyl R. Nicotinic receptor-mediated enhancement of long-term potentiation involves activation of metabotropic glutamate receptors and ryanodine-sensitive calcium stores in the dentate gyrus. Eur J Neurosci 24: 3109–3118, 2006.[CrossRef][Web of Science][Medline]
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
