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Patric K. Stanton - One of the best experts on this subject based on the ideXlab platform.
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Disabling Gβγ-SNAP-25 interaction in gene-targeted mice results in enhancement of long-term potentiation at Schaffer Collateral-CA1 synapses in the hippocampus.
Neuroreport, 2019Co-Authors: Muhammad Irfan, Zack Zurawski, Heidi E. Hamm, Christina Bark, Patric K. StantonAbstract:Three SNARE proteins, SNAP-25, syntaxin 1A, and VAMP2 or synaptobrevin 2, constitute the minimal functional machinery needed for the regulated secretion of neurotransmitters. Dynamic changes in the regulated release of neurotransmitters are associated with the induction of long-term plasticity at central synapses. In-vitro studies have validated the C-terminus of SNAP-25 as a target for inhibitory Gi/o-coupled G-protein coupled receptors at a number of synapses. The physiological consequences of the interaction between Gi/o proteins and SNAP-25 in the context of activity-dependent long-term synaptic plasticity are not well understood. Here, we report direct ex-vivo evidence of the involvement of the C-terminus of SNAP-25 in inducing long-term potentiation of synaptic strength at Schaffer Collateral-CA1 synapses using a gene-targeted mouse model with truncated C-terminus (carboxyl terminus) of SNAP-25. It has been shown previously that truncation of the three extreme C-terminal residues in SNAP-25[INCREMENT]3 homozygote mice reduces its interaction with the inhibitory Gβγ subunits two-fold. In in-vitro hippocampal slices, we show that these SNAP-25[INCREMENT]3 mice express significantly larger magnitude of long-term potentiation at hippocampal Schaffer Collateral-CA1 synapses.
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a nmda receptor glycine site partial agonist glyx 13 simultaneously enhances ltp and reduces ltd at Schaffer Collateral ca1 synapses in hippocampus
Neuropharmacology, 2008Co-Authors: Xiao-lei Zhang, John A Sullivan, Joseph R Moskal, Patric K. StantonAbstract:N-methyl-D-aspartate glutamate receptors (NMDARs) are a key route for Ca2+ influx into neurons important to both activity-dependent synaptic plasticity and, when uncontrolled, triggering events that cause neuronal degeneration and death. Among regulatory binding sites on the NMDAR complex is a glycine binding site, distinct from the glutamate binding site, which must be co-activated for NMDAR channel opening. We developed a novel glycine site partial agonist, GLYX-13, which is both nootropic and neuroprotective in vivo. Here, we assessed the effects of GLYX-13 on long-term synaptic plasticity and NMDAR transmission at Schaffer Collateral-CA1 synapses in hippocampal slices in vitro. GLYX-13 simultaneously enhanced the magnitude of long-term potentiation (LTP) of synaptic transmission, while reducing long-term depression (LTD). GLYX-13 reduced NMDA receptor-mediated synaptic currents in CA1 pyramidal neurons evoked by low frequency Schaffer Collateral stimulation, but enhanced NMDAR currents during high frequency bursts of activity, and these actions were occluded by a saturating concentration of the glycine site agonist d-serine. Direct two-photon imaging of Schaffer Collateral burst-evoked increases in [Ca2+] in individual dendritic spines revealed that GLYX-13 selectively enhanced burst-induced NMDAR-dependent spine Ca2+ influx. Examining the rate of MK-801 block of synaptic versus extrasynaptic NMDAR-gated channels revealed that GLYX-13 selectively enhanced activation of burst-driven extrasynaptic NMDARs, with an action that was blocked by the NR2B-selective NMDAR antagonist ifenprodil. Our data suggest that GLYX-13 may have unique therapeutic potential as a learning and memory enhancer because of its ability to simultaneously enhance LTP and suppress LTD.
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Gαi2 inhibition of adenylate cyclase regulates presynaptic activity and unmasks cGMP-dependent long-term depression at Schaffer Collateral-CA1 hippocampal synapses
Learning & memory (Cold Spring Harbor N.Y.), 2008Co-Authors: Chris Bailey, Russell E. Nicholls, Xiao-lei Zhang, Zhen-yu Zhou, Wolfgang Müller, Eric R. Kandel, Patric K. StantonAbstract:Cyclic AMP signaling plays a central role in regulating activity at a number of synapses in the brain. We showed previously that pairing activation of receptors that inhibit adenylate cyclase (AC) and reduce the concentration of cyclic AMP, with elevation of the concentration of cyclic GMP is sufficient to elicit a presynaptically expressed form of LTD at Schaffer Collateral-CA1 synapses in the hippocampus. To directly test the role of AC inhibition and G-protein signaling in LTD at these synapses, we utilized transgenic mice that express a mutant, constitutively active inhibitory G protein, Gαi2, in principal neurons of the forebrain. Transgene expression of Gαi2 markedly enhanced LTD and impaired late-phase LTP at Schaffer Collateral synapses, with no associated differences in input/output relations, paired-pulse facilitation, or NMDA receptor-gated conductances. When paired with application of a type V phosphodiesterase inhibitor to elevate the concentration of intracellular cyclic GMP, constitutively active Gαi2 expression converted the transient depression normally caused by this treatment to an LTD that persisted after the drug was washed out. Moreover, this effect could be mimicked in control slices by pairing type V phosphodiesterase inhibitor application with application of a PKA inhibitor. Electrophysiological recordings of spontaneous excitatory postsynaptic currents and two-photon visualization of vesicular release using FM1-43 revealed that constitutively active Gαi2 tonically reduced basal release probability from the rapidly recycling vesicle pool of Schaffer Collateral terminals. Our findings support the hypothesis that inhibitory G-protein signaling acts presynaptically to regulate release, and, when paired with elevations in the concentration of cyclic GMP, converts a transient cyclic GMP-induced depression into a long-lasting decrease in release.
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Comparison of cellular mechanisms of long-term depression of synaptic strength at perforant path-granule cell and Schaffer Collateral-CA1 synapses.
Progress in brain research, 2007Co-Authors: Beatrice Pöschel, Patric K. StantonAbstract:This chapter compares the cellular mechanisms that have been implicated in the induction and expression of long-term depression (LTD) at Schaffer Collateral-CA1 synapses to perforant path-dentate gyrus (DG) synapses. In general, Schaffer Collateral LTD and long-term potentiation (LTP) both appear to be a complex combination of many alterations in synaptic transmission that occur at both presynaptic and postsynaptic sites, while at perforant path synapses, most evidence has focused on postsynaptic long-term alterations. Within the DG, the medial perforant path is far more studied than lateral perforant path synapses, where most evidence relates to the induction of heterosynaptic LTD at lateral perforant path synapses when LTP is induced in the medial perforant path. Of course, there remain many other classes of synapses in the DG where synaptic plasticity, including LTD, have been largely neglected. It is clear that a better understanding of the range of DG loci where long-lasting activity-dependent plasticity, both LTD and LTP, are expressed will be essential to improve our understanding of the cognitive roles of such DG plasticity.
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nmda dependent but not group i metabotropic glutamate receptor dependent long term depression at Schaffer Collateral ca1 synapses is associated with long term reduction of release from the rapidly recycling presynaptic vesicle pool
The Journal of Neuroscience, 2006Co-Authors: Xiao-lei Zhang, Zhen-yu Zhou, Wolfgang Müller, Jochen Winterer, Patric K. StantonAbstract:Postsynaptic alterations have been suggested to account for NMDA receptor (NMDAR)-dependent long-term depression (LTD) and long-term potentiation of synaptic strength, although there is substantial evidence supporting changes in presynaptic release. Direct chemical activation of either NMDA or group I metabotropic glutamate receptor (mGluR1) elicits LTD of similar magnitudes, but it is unknown whether they share common expression mechanisms. Using dual-photon laser-scanning microscopy of FM1-43 [ N -(3-triethylammoniumpropyl)-4-(4-(dibutylamino)styryl)pyridinium dibromide] to directly visualize presynaptic vesicular release from the rapidly recycling vesicle pool (RRP) at Schaffer Collateral terminals in field CA1 of rat hippocampal slices, we found that a persistent reduction in vesicular release from the RRP is induced by NMDA-LTD but not by mGluR1-LTD. Variance-mean analyses of Schaffer Collateral release probability ( P r ) at varying extracellular calcium concentrations confirmed that NMDA-LTD was associated with reduced P r , whereas mGluR1-LTD was not. Pharmacological isolation of NMDAR-dependent and mGluR-dependent forms of stimulus-evoked LTD revealed that both are composed of a combination of presynaptic and postsynaptic alterations. However, when group I mGluR-dependent LTD was isolated by combining an NMDAR blocker with a group II mGluR antagonist, this form of LTD was purely postsynaptic. The nitric oxide synthase inhibitor Nω-nitro-l-arginine blocked the induction of NMDA-LTD but did not alter mGluR-LTD, consistent with a selective role for nitric oxide as a retrograde messenger mediating NMDA-LTD. These data demonstrate that single synapses can express multiple forms of LTD with different sites of expression, that NMDA-LTD is a combination of presynaptic and postsynaptic alterations, but that group I mGluR-LTD appears to be expressed entirely postsynaptically.
Lianjun Guo - One of the best experts on this subject based on the ideXlab platform.
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low dose zd7288 attenuates the ischemia reperfusion induced impairment of long term potentiation induction at hippocampal Schaffer Collateral ca1 synapses
Cellular and Molecular Neurobiology, 2014Co-Authors: Lianjun GuoAbstract:Focal cerebral ischemia can impair the induction of activity-dependent long-term potentiation (LTP) in the hippocampus. This impairment of hippocampal synaptic plasticity can be caused by excitotoxicity and subsequent perturbation of hippocampal LTP-relevant transmitter systems, which include NR2B and PSD-95. It has been suggested that hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels may play an important role in the control of membrane excitability and rhythmic neuronal activity. Our previous study has indicated that the selective HCN channel blocker ZD7288 can produce a dose-dependent inhibition of the induction of LTP at the Schaffer Collateral-CA1 synapse of hippocampus by reducing the amount of glutamate released. It has also been demonstrated that ZD7288 can protect against neuronal injury caused by oxygen glucose deprivation. In the present study, we investigated the effect of ZD7288 on the induction of activity-dependent LTP and the expression of NR2B and PSD-95 after focal cerebral ischemia/reperfusion injury. The results showed that the induction of LTP was significantly impaired and the levels of NR2B and PSD-95 mRNA and protein were markedly decreased in the CA1 region of hippocampus following focal cerebral ischemia/reperfusion injury. Administration of low dose ZD7288 (0.25 μg) at 30 min and 3 h after the onset of ischemia attenuated the impairment of LTP induction and alleviated the NR2B and PSD-95 mRNA and protein down-regulation commonly induced by cerebral ischemia/reperfusion injury. These results suggest that low dose ZD7288 can ameliorate the ischemia/reperfusion-induced impairment of synaptic plasticity in the hippocampal CA1 region.
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Clonidine suppresses the induction of long-term potentiation by inhibiting HCN channels at the Schaffer Collateral-CA1 synapse in anesthetized adult rats.
Cellular and molecular neurobiology, 2013Co-Authors: Mei Zhou, Lianjun GuoAbstract:Activation of alpha2-adrenoceptors inhibits long-term potentiation and long-term depression in many brain regions. However, effectiveness and mechanism of alpha2-adrenoceptors for synaptic plasticity at the Schaffer Collateral–CA1 synapses in rat in vivo is unclear. In the present study, we investigated the effects of alpha2-adrenoceptors agonist clonidine on high-frequency stimulation (HFS)-induced long-term potentiation (LTP) and paired-pulse facilitation (PPF) at the Schaffer Collateral–CA1 synapse of rat hippocampus in vivo. Clonidine (0.05, 0.1 mg/kg, ip) inhibited synaptic plasticity in a dose-dependent manner, accompanying with the decreasing of aortic pressure and heart rate (HR) in anesthetized rats. Clonidine (1.25, 2.5 μg/kg, icv, 10 min before HFS) also dose-dependently inhibited synaptic plasticity, which had no remarkable effect on HR and aortic pressure. But, 20 min after HFS, administration of clonidine (2.5 μg/kg) had no effect on LTP. The inhibitory effect of clonidine (2.5 μg/kg) on LTP was completely reversed by yohimbine (18 μg/kg, icv) and ZD7288 (5 μg/kg, icv). Moreover, the inhibition was accompanied by a significant increase of the normalized PPF ratio. Furthermore, clonidine at 1 and 10 μM significantly decreased glutamate (Glu) content in the culture supernatants of hippocampal neurons, and yohimbine at 1 and 10 μM had no effect on Glu release, while it could reverse the inhibition of clonidine (1 and 10 μM) on Glu release. In conclusion, clonidine can suppress the induction of LTP at the Schaffer Collateral–CA1 synapse, and the possible mechanism is that activation of presynaptic alpha2-adrenoceptors reduces the Glu release by inhibiting HCN channels.
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ZD7288-induced suppression of long-term potentiation was attenuated by exogenous NMDA at the Schaffer Collateral-CA1 synapse in the rat in vivo.
European journal of pharmacology, 2010Co-Authors: Zhenyong Cheng, Lianjun GuoAbstract:Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels have been suggested to play an important role in the control of membrane excitability and rhythmic neuronal activity. Our previous study showed that the selective HCN channels blocker, ZD7288 (4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride) can block the induction of long-term potentiation (LTP) in perforant path-CA3 region in rat hippocampus in vivo. In the present study, we investigated the effect of ZD7288 on synaptic transmission and high frequency stimulation (HFS)-induced LTP in the Schaffer Collateral-CA1 synapse of rat hippocampus in vivo, and examined the possible relations between activation of N-methyl-d-aspartate (NMDA) type of glutamate receptor and HCN channels for induction of LTP. Application of ZD7288 modulated synaptic transmission and produced a dose-dependent inhibition of the induction of LTP, and the inhibitory action was partially reversed by the application of NMDA. In addition, ZD7288, when given 30 min after HFS, did not alter the maintenance of LTP. The results suggest that ZD7288 has the ability to prevent the induction of LTP at the Schaffer Collateral-CA1 synapse of rat hippocampus, and that this inhibitory effect is attenuated by direct activation of the NMDA receptor.
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ZD7288-induced suppression of long-term potentiation was attenuated by exogenous NMDA at the Schaffer Collateral–CA1 synapse in the rat in vivo
European Journal of Pharmacology, 2010Co-Authors: Zhenyong Cheng, Lianjun GuoAbstract:Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels have been suggested to play an important role in the control of membrane excitability and rhythmic neuronal activity. Our previous study showed that the selective HCN channels blocker, ZD7288 (4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride) can block the induction of long-term potentiation (LTP) in perforant path-CA3 region in rat hippocampus in vivo. In the present study, we investigated the effect of ZD7288 on synaptic transmission and high frequency stimulation (HFS)-induced LTP in the Schaffer Collateral-CA1 synapse of rat hippocampus in vivo, and examined the possible relations between activation of N-methyl-d-aspartate (NMDA) type of glutamate receptor and HCN channels for induction of LTP. Application of ZD7288 modulated synaptic transmission and produced a dose-dependent inhibition of the induction of LTP, and the inhibitory action was partially reversed by the application of NMDA. In addition, ZD7288, when given 30 min after HFS, did not alter the maintenance of LTP. The results suggest that ZD7288 has the ability to prevent the induction of LTP at the Schaffer Collateral-CA1 synapse of rat hippocampus, and that this inhibitory effect is attenuated by direct activation of the NMDA receptor.
Charles F. Zorumski - One of the best experts on this subject based on the ideXlab platform.
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Temperoammonic Stimulation Depotentiates Schaffer Collateral LTP via p38 MAPK Downstream of Adenosine A1 Receptors.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2019Co-Authors: Yukitoshi Izumi, Charles F. ZorumskiAbstract:We previously found that low-frequency stimulation of direct temperoammonic (TA) inputs to hippocampal area CA1 depotentiates previously established long-term potentiation in the Schaffer Collateral (SC) pathway through complex signaling involving dopamine, endocannabinoids, neuregulin-1, GABA, and adenosine, with adenosine being the most distal modulator identified to date. In the present studies, we examined mechanisms contributing to the effects of adenosine in hippocampal slices from male albino rats. We found that extracellular conversion of ATP to adenosine via an ectonucleotidase contributes significantly to TA-mediated SC depotentiation and the depotentiation resulting from block of adenosine transport. Adenosine-mediated SC depotentiation does not involve activation of c-Jun N-terminal protein kinase, serine phosphatases, or nitric oxide synthase, unlike homosynaptic SC depotentiation. Rather, adenosine-induced depotentiation is inhibited by specific antagonists of p38 MAPK, but not by a structural analog that does not inhibit p38. Additionally, using antagonists with relative selectivity for p38 subtypes, it appears that TA-induced SC depotentiation most likely involves p38 MAPK β. These findings have implications for understanding the role of adenosine and other extrahippocampal and intrahippocampal modulators in regulating SC synaptic function and the contributions of these modulators to the cognitive dysfunction associated with neuropsychiatric illnesses. SIGNIFICANCE STATEMENT Low-frequency stimulation of temperoammonic (TA) inputs to stratum lacunosum moleculare of hippocampal area CA1 heterosynaptically depotentiates long-term potentiation of Schaffer Collateral (SC) synapses. TA-induced SC depotentiation involves complex signaling including dopamine, endocannabinoids, GABA, and adenosine, with adenosine serving as the most downstream messenger in the cascade identified to date. The present results indicate that TA-induced depotentiation requires intact inputs from entorhinal cortex and that adenosine ultimately drives depotentiation via activation of p38 MAPK. These studies have implications for understanding the cognitive dysfunction of psychiatric illnesses and certain abused drugs.
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Neuregulin and Dopamine D4 Receptors Contribute Independently to Depotentiation of Schaffer Collateral LTP by Temperoammonic Path Stimulation.
eNeuro, 2017Co-Authors: Yukitoshi Izumi, Charles F. ZorumskiAbstract:Abstract Prior studies have found that dopamine (DA), acting at D4 receptors, and neuregulin (NRG), likely acting at ErbB4 receptors, are involved in a form of depotentiation of long-term potentiation (LTP) at Schaffer Collateral (SC) synapses in the hippocampus. Furthermore, DA and NRG actions are intertwined in that NRG induces DA release. We previously found that low-frequency stimulation (LFS) of temperoammonic (TA) inputs to area CA1 also depotentiates previously established SC LTP through a complex signaling pathway involving endocannabinoids, GABA, adenosine, and mitogen-activated protein kinases (MAPKs), but not glutamate. In the present studies, we found that TA-induced SC depotentiation in hippocampal slices from Sprague-Dawley albino rats also involves activation of both D4 receptors and NRG-activated ErbB receptors, but that the roles of these two modulator systems are independent with D4 receptor antagonism failing to alter chemical depotentiation by NRG1β. Furthermore, a selective D4 receptor agonist was unable to depotentiate SC LTP when administered alone, suggesting that D4 receptor activation is necessary but not sufficient for TA-induced SC depotentiation. Chemical depotentiation by NRG1β was inhibited by a Pan-ErbB antagonist and by picrotoxin (PTX), an antagonist of GABA-A receptors (GABA A Rs), indicating that NRG likely promotes SC depotentiation via effects on GABA and interneurons. These findings have implications for understanding the role of DA and NRG in cognitive dysfunction associated with neuropsychiatric illnesses.
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GABA and Endocannabinoids Mediate Depotentiation of Schaffer Collateral Synapses Induced by Stimulation of Temperoammonic Inputs
PloS one, 2016Co-Authors: Yukitoshi Izumi, Charles F. ZorumskiAbstract:Long-term potentiation (LTP) of Schaffer Collateral (SC) synapses in the hippocampus is thought to play a key role in episodic memory formation. Because the hippocampus is a shorter-term, limited capacity storage system, repeated bouts of learning and synaptic plasticity require that SC synapses reset to baseline at some point following LTP. We previously showed that repeated low frequency activation of temperoammonic (TA) inputs to the CA1 region depotentiates SC LTP without persistently altering basal transmission. This heterosynaptic depotentiation involves adenosine A1 receptors but not N-methyl-D-aspartate receptors, metabotropic glutamate receptors or L-type calcium channels. In the present study, we used rat hippocampal slices to explore other messengers contributing to TA-induced SC depotentiation, and provide evidence for the involvement of cannabinoid-1 and γ-aminobutyric acid (GABA) type-A receptors as more proximal signaling events leading to synaptic resetting, with A1 receptor activation serving as a downstream event. Surprisingly, we found that TA-induced SC depotentiation is independent of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate glutamate receptors. We also examined the involvement of mitogen-activated protein kinases (MAPKs), and found a role for extracellular-signal related kinase 1/2 and p38 MAPK, but not c-Jun-N-terminal kinase. These results indicate that low frequency stimulation of TA inputs to CA1 activates a complex signaling network that instructs SC synaptic resetting. The involvement of GABA and endocannabinoids suggest mechanisms that could contribute to cognitive dysfunction associated with substance abuse and neuropsychiatric disorders.
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Direct Cortical Inputs Erase Long-Term Potentiation at Schaffer Collateral Synapses
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008Co-Authors: Yukitoshi Izumi, Charles F. ZorumskiAbstract:Long-term potentiation (LTP), a synaptic mechanism thought to underlie memory formation, has been studied extensively at hippocampal Schaffer Collateral (SC) synapses. The SC pathway transmits information to area CA1 that originates in entorhinal cortex and is processed by the dentate gyrus and area CA3. CA1 also receives direct excitatory input from entorhinal cortex via the perforant path (PP), but the role of this cortical input is less certain. Here, we report that low-frequency stimulation of PP inputs to CA1 has no lasting effect on basal SC transmission, but effectively depotentiates SC synapses that have undergone LTP in a manner that can be reversed by subsequent high-frequency stimulation of SC inputs. This depotentiation does not require NMDA receptors, group I metabotropic glutamate receptors, or L-type calcium channels, but involves adenosine acting at A 1 receptors. Given the limited storage capacity of the hippocampus, these observations provide a mechanism by which input from cortex can help to reset synaptic transmission in the hippocampus and facilitate additional information processing.
Jian-hao Cheng - One of the best experts on this subject based on the ideXlab platform.
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effects of uninterrupted sinusoidal lf emf stimulation on ltp induced by different combinations of tbs hfs at the Schaffer Collateral ca1 of synapses
Brain Research, 2019Co-Authors: Yu Zheng, Lei Dong, Jian-hao ChengAbstract:Abstract Long-term potentiation (LTP) is an important aspect of synaptic plasticity and is one of the main mechanisms involved in memory. Low-frequency electromagnetic fields (LF-EMFs) such as transcranial magnetic stimulation are emerging neuromodulation tools for the regulation of LTP. However, whether LF-EMFs have different effects on different types of LTP has not yet been verified. Herein, we studied the regulatory effects of 15 Hz/2 mT sinusoidal magnetic field as pre-magnetic stimulation on several types of LTP, which were induced by theta-burst(TBS) or high-frequency stimulation (HFS) or some combination of them, and applied N-methyl-D-aspartate receptor(NMDAR) antagonists to observe the relationship between the regulation of LTP by LF-EMFs and NMDAR in the Schaffer Collateral pathway of rat brain slices in vitro. The results presented in this paper are the performance of TBS and HFS was not exactly the same and the recovery speed of TBS-LTP was faster than HFS-LTP after receiving the regulation of LF-EMFs; moreover, the LTP level was affected by the order of combination and the effect of pre-magnetic stimulation could maintain the entire process of the combined induction experiment, while NMDAR antagonists could not completely offset the influence of LF-EMFs. The memory patterns are diverse, and this study has shown LF-EMFs can regulate LTP such as TBS-LTP and HFS-LTP and can continuously affect multiple LTP induction processes. However, different memory processes may have different performance in the face of LF-EMFs regulation. In terms of the mechanism of LF-EMFs-induced LTP regulation, NMDARs may be involved in the process of LF-EMF regulation of LTP, but are not the only factor.
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Effects of uninterrupted sinusoidal LF-EMF stimulation on LTP induced by different combinations of TBS/HFS at the Schaffer Collateral-CA1 of synapses.
Brain research, 2019Co-Authors: Yu Zheng, Lei Dong, Jian-hao ChengAbstract:Abstract Long-term potentiation (LTP) is an important aspect of synaptic plasticity and is one of the main mechanisms involved in memory. Low-frequency electromagnetic fields (LF-EMFs) such as transcranial magnetic stimulation are emerging neuromodulation tools for the regulation of LTP. However, whether LF-EMFs have different effects on different types of LTP has not yet been verified. Herein, we studied the regulatory effects of 15 Hz/2 mT sinusoidal magnetic field as pre-magnetic stimulation on several types of LTP, which were induced by theta-burst(TBS) or high-frequency stimulation (HFS) or some combination of them, and applied N-methyl-D-aspartate receptor(NMDAR) antagonists to observe the relationship between the regulation of LTP by LF-EMFs and NMDAR in the Schaffer Collateral pathway of rat brain slices in vitro. The results presented in this paper are the performance of TBS and HFS was not exactly the same and the recovery speed of TBS-LTP was faster than HFS-LTP after receiving the regulation of LF-EMFs; moreover, the LTP level was affected by the order of combination and the effect of pre-magnetic stimulation could maintain the entire process of the combined induction experiment, while NMDAR antagonists could not completely offset the influence of LF-EMFs. The memory patterns are diverse, and this study has shown LF-EMFs can regulate LTP such as TBS-LTP and HFS-LTP and can continuously affect multiple LTP induction processes. However, different memory processes may have different performance in the face of LF-EMFs regulation. In terms of the mechanism of LF-EMFs-induced LTP regulation, NMDARs may be involved in the process of LF-EMF regulation of LTP, but are not the only factor.
Lynn E Dobrunz - One of the best experts on this subject based on the ideXlab platform.
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developmental changes in short term facilitation are opposite at temporoammonic synapses compared to Schaffer Collateral synapses onto ca1 pyramidal cells
Hippocampus, 2009Co-Authors: Haley E Speed, Lynn E DobrunzAbstract:CA1 pyramidal neurons receive two distinct excitatory inputs that are each capable of influencing hippocampal output and learning and memory. The Schaffer Collateral (SC) input from CA3 axons onto the more proximal dendrites of CA1 is part of the trisynaptic circuit, which originates in Layer II of the entorhinal cortex (EC). The temporoammonic (TA) pathway to CA1 provides input directly from Layer III of the EC onto the most distal dendrites of CA1 pyramidal cells, and is involved in spatial memory and memory consolidation. We have previously described a developmental decrease in short-term facilitation from juvenile (P13-18) to young adult (P28-42) rats at SC synapses that is due to feedback inhibition via synaptically activated mGluR1 on CA1 interneurons. It is not known how short-term changes in synaptic strength are regulated at TA synapses, nor is it known how short-term plasticity is balanced at SC and TA inputs during development. Here we describe a novel developmental increase in short-term facilitation at TA synapses, which is the opposite of the decrease in facilitation occurring at SC synapses. Although short-term facilitation is much lower at TA synapses when compared with SC synapses in juveniles, short-term plasticity at SC and TA synapses converges at similar levels of paired-pulse facilitation in the young adult rat. However, in young adults CA3-CA1 synapses still exhibit more facilitation than TA-CA1 synapses during physiologically-relevant activity, suggesting that the two pathways are each poised to uniquely modulate CA1 output in an activity-dependent manner. Finally, we show that there is a developmental decrease in the initial release probability at TA synapses that underlies their developmental decrease in facilitation, but no developmental change in release probability at SC synapses. This represents a fundamental difference in the presynaptic function of the two major inputs to CA1, which could alter the flow of information in hippocampus during development.
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presynaptic kainate receptor activation is a novel mechanism for target cell specific short term facilitation at Schaffer Collateral synapses
The Journal of Neuroscience, 2006Co-Authors: Hua Yu Sun, Lynn E DobrunzAbstract:Target cell-specific differences in short-term plasticity have been attributed to differences in the initial release probability of synapses. Using GIN (GFP-expressing inhibitory neurons) transgenic mice that express enhanced green fluorescent protein (EGFP) in a subset of interneurons containing somatostatin, we show that Schaffer Collateral synapses onto the EGFP-expressing somatostatin interneurons in CA1 have very large short-term facilitation, even larger facilitation than onto pyramidal cells, in contrast to the majority of interneurons that have little or no facilitation. Using a combination of electrophysiological recordings and mathematical modeling, we show that the large short-term facilitation is caused both by a very low initial release probability and by synaptic activation of presynaptic kainate receptors that increase release probability on subsequent stimuli. Thus, we have discovered a novel mechanism for target cell-specific short-term plasticity at Schaffer Collateral synapses in which the activation of presynaptic kainate receptors by synaptically released glutamate contributes to large short-term facilitation, enabling selective enhancement of the inputs to a subset of interneurons.
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Mechanisms of target-cell specific short-term plasticity at Schaffer Collateral synapses onto interneurones versus pyramidal cells in juvenile rats
The Journal of Physiology, 2005Co-Authors: Hua Yu Sun, Susan A. Lyons, Lynn E DobrunzAbstract:Although it is presynaptic, short-term plasticity has been shown at some synapses to depend upon the postsynaptic cell type. Previous studies have reported conflicting results as to whether Schaffer Collateral axons have target-cell specific short-term plasticity. Here we investigate in detail the short-term dynamics of Schaffer Collateral excitatory synapses onto CA1 stratum radiatum interneurones versus pyramidal cells in acute hippocampal slices from juvenile rats. In response to three stimulus protocols that invoke different forms of short-term plasticity, we find differences in some but not all forms of presynaptic short-term plasticity, and heterogeneity in the short term plasticity of synapses onto interneurones. Excitatory synapses onto the majority of interneurones had less paired-pulse facilitation than synapses onto pyramidal cells across a range of interpulse intervals (20–200 ms). Unlike synapses onto pyramidal cells, synapses onto most interneurones had very little facilitation in response to short high-frequency trains of five pulses at 5, 10 and 20 Hz, and depressed during trains at 50 Hz. However, the amount of high-frequency depression was not different between synapses onto pyramidal cells versus the majority of interneurones at steady state during 2–10 Hz trains. In addition, a small subset of interneurones (approximately 15%) had paired-pulse depression rather than paired-pulse facilitation, showed only depression in response to the high-frequency five pulse trains, and had more steady-state high-frequency depression than synapses onto pyramidal cells or the majority of interneurones. To investigate possible mechanisms for these differences in short-term plasticity, we developed a mechanistic mathematical model of neurotransmitter release that explicitly explores the contributions to different forms of short-term plasticity of the readily releasable vesicle pool size, release probability per vesicle, calcium-dependent facilitation, synapse inactivation following release, and calcium-dependent recovery from inactivation. Our model fits the responses of each of the three cell groups to the three different stimulus protocols with only two parameters that differ with cell group. The model predicts that the differences in short-term plasticity between synapses onto CA1 pyramidal cells and stratum radiatum interneurones are due to a higher initial release probability per vesicle and larger readily releasable vesicle pool size at synapses onto interneurones, resulting in a higher initial release probability. By measuring the rate of block of NMDA receptors by the open channel blocker MK-801, we confirmed that the initial release probability is greater at synapses onto interneurones versus pyramidal cells. This provides a mechanism by which both the initial strength and the short-term dynamics of Schaffer Collateral excitatory synapses are regulated by their postsynaptic target cell.
