scholarly journals Status Epilepticus Enhances Depotentiation after Fully Established LTP in an NMDAR-Dependent but GluN2B-Independent Manner

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Xiati Guli ◽  
Tursonjan Tokay ◽  
Timo Kirschstein ◽  
Rüdiger Köhling
Keyword(s):  
Status Epilepticus ◽  
Nmda Receptor ◽  
Low Frequency ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Nmda Receptor Antagonist ◽  
Independent Manner ◽  
Ca1 Neurons ◽  
Term Potentiation ◽  
Frequency Stimulation

N-Methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) can be reversed by low-frequency stimulation (LFS) referred to as depotentiation (DP). We previously found GluN2B upregulated in CA1 neurons from post-status epilepticus (post-SE) tissue associated with an enhanced LTP. Here, we tested whether LFS-induced DP is also altered in pathological GluN2B upregulation. Although LTP was enhanced in post-SE tissue, LTP was significantly reversed in this tissue, but not in controls. We next tested the effect of the GluN2B subunit-specific blocker Ro 25-6981 (1 μM) on LFS-DP. As expected, LFS had no effect on synaptic strength in the presence of the GluN2B blocker in control tissue. In marked contrast, LFS-DP was also attained in post-SE tissue indicating that GluN2B was obviously not involved in depotentiation. To test for NMDA receptor-dependence, we applied the NMDA receptor antagonist D-AP5 (50 μM) prior to LFS and observed that DP was abolished in both control and post-SE tissue confirming NMDA receptor involvement. These results indicate that control Schaffer collateral-CA1 synapses cannot be depotentiated after fully established LTP, but LFS was able to reverse LTP significantly in post-SE tissue. However, while LFS-DP clearly required NMDA receptor activation, GluN2B-containing NMDA receptors were not involved in this form of depotentiation.

Coexistence of Muscarinic Long-Term Depression With Electrically Induced Long-Term Potentiation and Depression at CA3–CA1 Synapses

2006 ◽  
Vol 96 (6) ◽  
pp. 3114-3121 ◽  
Author(s):  
Eve McCutchen ◽  
Cary L. Scheiderer ◽  
Lynn E. Dobrunz ◽  
Lori L. McMahon
Keyword(s):  
Synaptic Plasticity ◽  
Low Frequency ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
High Frequency Stimulation ◽  
Muscarinic Agonist ◽  
Long Term Depression ◽  
Term Potentiation ◽  
Frequency Stimulation

Our laboratory recently characterized a form of long-term depression (LTD) at CA3–CA1 synapses mediated by M1 muscarinic receptors (mAChRs), termed muscarinic LTD (mLTD). mLTD is both activity and NMDAR dependent, characteristics shared by forms of synaptic plasticity thought to be relevant to learning and memory, including long-term potentiation (LTP) induced by high-frequency stimulation (HFS-LTP) and long-term depression induced by low-frequency stimulation (LFS-LTD). However, it remains unclear whether mLTD can occur sequentially with these electrically induced forms of hippocampal plasticity or whether mLTD might interact with them. The first goal of this study was to examine the interplay of mLTD and HFS-LTP. We report that mLTD expression does not alter subsequent induction of HFS-LTP and, further, at synapses expressing HFS-LTP, mLTD can mediate a novel form of depotentiation. The second goal was to determine whether mLTD would alter LFS-LTD induction and/or expression. Although we show that mLTD is occluded by saturation of LFS-LTD, suggesting mechanistic similarity between these two plasticities, saturation of mLTD does not occlude LFS-LTD. Surprisingly, however, the LFS-LTD that follows cholinergic receptor activation is NMDAR independent, indicating that application of muscarinic agonist induces a change in the induction mechanism required for LFS-LTD. These data demonstrate that mLTD can coexist with electrically induced forms of synaptic plasticity and support the hypothesis that mLTD is one of the mechanisms by which the cholinergic system modulates hippocampal function.

Calcium signals in long-term potentiation and long-term depression

1999 ◽  
Vol 77 (9) ◽  
pp. 722-734 ◽  
Author(s):  
John A Connor ◽  
Jeffrey Petrozzino ◽  
Lucas D Pozzo-Miller ◽  
Satoru Otani
Keyword(s):  
Nmda Receptor ◽  
Neuronal Plasticity ◽  
Hippocampal Neurons ◽  
Low Frequency ◽  
Long Term Potentiation ◽  
Long Term Depression ◽  
Metabotropic Receptor ◽  
Ca1 Neurons ◽  
Term Potentiation

We describe postsynaptic Ca2+ signals that subserve induction of two forms of neuronal plasticity, long-term potentiation (LTP) and long-term depression (LTD), in rat hippocampal neurons. The common induction protocol for LTP, a 1-s, 50-Hz tetanus, generates Ca2+ increases of about 50 µM in dendritic spines of CA1 neurons. These very large increases, measured using a low affinity indicator (Mg fura 5), were found only in the spines and tertiary dendrites, and were dependent upon influx through N-methyl-D-aspartate (NMDA) gated channels. High affinity Ca2+ indicators (e.g., fura 2) are unable to demonstrate these events. In acute slices, neighboring dendritic branches often showed very different responses to a tetanus, and in some instances, neighboring spines on the same dendrite responded differently. LTD in mature CA1 neurons was induced by a low frequency stimulus protocol (2 Hz, 900 pulses), in the presence of GABA- and NMDA-receptor blockers. This LTD protocol produced dendritic Ca2+ increases of <1 µM. Duration of the Ca2+ increase was ~30 s and was due to voltage-gated Ca2+ influx. Finally, the ability of synaptically addressed Ca2+ stores to release Ca2+ was studied in CA3 neurons and was found to require immediate preloading and high intensity presynaptic stimulation, conditions unlike normal LTP-LTD protocols.Key words: long-term potentiation, long-term depression, Ca2+, neuronal plasticity, fluorescence imaging, N-methyl-D-aspartate (NMDA) receptor, metabotropic receptor.

Reexamination of the effects of MCPG on hippocampal LTP, LTD, and depotentiation

1995 ◽  
Vol 74 (3) ◽  
pp. 1075-1082 ◽  
Author(s):  
D. K. Selig ◽  
H. K. Lee ◽  
M. F. Bear ◽  
R. C. Malenka
Keyword(s):  
Hippocampal Neurons ◽  
Metabotropic Glutamate Receptor ◽  
Low Frequency ◽  
Extracellular Recording ◽  
Pyramidal Cells ◽  
Long Term Potentiation ◽  
Metabotropic Glutamate ◽  
Term Potentiation ◽  
Frequency Stimulation

1. We examined the effects of the metabotropic glutamate receptor (mGluR) antagonist alpha-methyl-4-carboxyphenylglycine (MCPG) on the induction of long-term potentiation (LTP) long-term depression (LTD), and depotentiation in CA1 hippocampal neurons using extracellular recording techniques. 2. MCPG (500 microM) strongly antagonized the presynaptic inhibitory action of the mGluR agonist 1-aminocyclopentane-(1S,3R)-dicarboxylic acid yet failed to block LTP induced with either tetanic stimulation (100 Hz, 1 s) or theta-burst stimulation. 3. To test the possibility that our failure to block LTP was due to prior activation of a "molecular switch" that in its "on" state obviates the need for mGluR activation to generate LTP, we gave repeated periods of prolonged low-frequency stimulation (LFS; 1 Hz, 10 min), a manipulation reported to turn the switch "off." Although this stimulation saturated LTD, subsequent application of MCPG still failed to block LTP. 4. MCPG did not block LFS-induced depotentiation in older slices (4-6 wk) or LFS-induced LTD in older, young (11-18 days), or neonatal (3-7 days) slices. 5. These results demonstrate that MCPG-sensitive mGluRs are not necessary for the induction of LTP, LTD, or depotentiation in hippocampal CA1 pyramidal cells. The possibility remains, however, that their activation may modify the threshold for the induction of these long-term plastic changes.

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