scholarly journals Selective Abolition of the NMDA Component of Long-Term Potentiation in Mice Lacking mGluR5

1998 ◽  
Vol 5 (4) ◽  
pp. 331-343
Author(s):  
Zhengping Jia ◽  
YouMing Lu ◽  
Jeff Henderson ◽  
Franco Taverna ◽  
Carmelo Romano ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Long Term Potentiation ◽  
Mutant Mice ◽  
Excitatory Postsynaptic Potential ◽  
Metabotropic Glutamate ◽  
Term Potentiation

The mechanisms underlying the differential expression of long-term potentiation (LTP) by AMPA and NMDA receptors, are unknown, but could involve G-protein-linked metabotropic glutamate receptors. To investigate this hypothesis we created mutant mice that expressed no metabotropic glutamate receptor 5 (mGluR5), but showed normal development. In an earlier study of these mice we analyzed field-excitatory postsynaptic potential (fEPSPs) in CA1 region of the hippocampus and found a small decrease; possibly arising from changes in the NMDAR-mediated component of synaptic transmission. In the present study we used whole-cell patch clamp recordings of evoked excitatory postsynaptic currents (EPSCs) in CA1 pyramidal neurons to identify the AMPAR- and NMDAR-mediated components of LTP. Recordings from control mice following tetanus, or agonist application (IS, 3R-1-amino-cyclopentane 1,3-dicarboxylic acid) (ACPD), revealed equal enhancement of the AMPA and NMDA receptor-mediated components. In contrast, CA1 neurons from mGluR5-deficient mice showed a complete loss of the NMDA-receptor-mediated component of LTP (LTPNMDA), but normal LTP of the AMPA-receptor-mediated component (LTPAMPA). This selective loss of LTPNMDA was seen in three different genotypic backgrounds and was apparent at all holding potentials (−70 mV to +20 mV). Furthermore, the LTPNMDA deficit in mGluR5 mutant mice could be rescued by stimulating protein kinase C (PKC) with 4β-phorbol-12,13-dibutyrate (PDBu). These results suggest that PKC may couple the postsynaptic mGluR5 to the NMDA-receptor potentiation during LTP, and that this signaling mechanism is distinct from LTPAMPA. Differential enhancement of AMPAR and NMDA receptors by mGluR5 also supports a postsynaptic locus for LTP.

scholarly journals NMDA Receptor-Dependent Metaplasticity by High-Frequency Magnetic Stimulation

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Tursonjan Tokay ◽  
Timo Kirschstein ◽  
Marco Rohde ◽  
Volker Zschorlich ◽  
Rüdiger Köhling
Keyword(s):  
Nmda Receptor ◽  
High Frequency ◽  
Magnetic Stimulation ◽  
Metabotropic Glutamate Receptor ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Excitatory Postsynaptic Potential ◽  
Metabotropic Glutamate

High-frequency magnetic stimulation (HFMS) can elicit N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) at Schaffer collateral-CA1 pyramidal cell synapses. Here, we investigated the priming effect of HFMS on the subsequent magnitude of electrically induced LTP in the CA1 region of rat hippocampal slices using field excitatory postsynaptic potential (fEPSP) recordings. In control slices, electrical high-frequency conditioning stimulation (CS) could reliably induce LTP. In contrast, the same CS protocol resulted in long-term depression when HFMS was delivered to the slice 30 min prior to the electrical stimulation. HFMS-priming was diminished when applied in the presence of the metabotropic glutamate receptor antagonists (RS)-α-methylserine-O-phosphate (MSOP) and (RS)-α-methyl-4-carboxyphenylglycine (MCPG). Moreover, when HFMS was delivered in the presence of the NMDA receptor-antagonist D-2-amino-5-phosphonovalerate (50 µM), CS-induced electrical LTP was again as high as under control conditions in slices without priming. These results demonstrate that HFMS significantly reduced the propensity of subsequent electrical LTP and show that both metabotropic glutamate and NMDA receptor activation were involved in this form of HFMS-induced metaplasticity.

Insights into associative long-term potentiation from computational models of NMDA receptor-mediated calcium influx and intracellular calcium concentration changes

1990 ◽  
Vol 63 (5) ◽  
pp. 1148-1168 ◽  
Author(s):  
W. R. Holmes ◽  
W. B. Levy
Keyword(s):  
Experimental Data ◽  
Nmda Receptor ◽  
Nmda Receptors ◽  
Dendritic Spine ◽  
Long Term Potentiation ◽  
Input Frequency ◽  
Spine Head ◽  
Term Potentiation ◽  
Concentration Changes

1. Because induction of associative long-term potentiation (LTP) in the dentate gyrus is thought to depend on Ca2+ influx through channels controlled by N-methyl-D-aspartate (NMDA) receptors, quantitative modeling was performed of synaptically mediated Ca2+ influx as a function of synaptic coactivation. The goal was to determine whether Ca2+ influx through NMDA-receptor channels was, by itself, sufficient to explain associative LTP, including control experiments and the temporal requirements of LTP. 2. Ca2+ influx through NMDA-receptor channels was modeled at a synapse on a dendritic spine of a reconstructed hippocampal dentate granule cell when 1-115 synapses on spines at different dendritic locations were activated eight times at frequencies of 10-800 Hz. The resulting change in [Ca2+] in the spine head was estimated from the Ca2+ influx with the use of a model of a dendritic spine that included Ca2+ buffers, pumps, and diffusion. 3. To use a compelling model of synaptic activation, we developed quantitative descriptions of the NMDA and non-NMDA receptor-mediated conductances consistent with available experimental data. The experimental data reported for NMDA and non-NMDA receptor-channel properties and data from other non-LTP experiments that separated the NMDA and non-NMDA receptor-mediated components of synaptic events proved to be limiting for particular synaptic variables. Relative to the non-NMDA glutamate-type receptors, 1) the unbinding of transmitter from NMDA receptors had to be slow, 2) the transition from the bound NMDA receptor-transmitter complex to the open channel state had to be even slower, and 3) the average number of NMDA-receptor channels at a single activated synapse on a single spine head that were open and conducting at a given moment in time had to be very small (usually less than 1). 4. With the use of these quantitative synaptic conductance descriptions. Ca2+ influx through NMDA-receptor channels at a synapse was computed for a variety of conditions. For a constant number of pulses, Ca2+ influx was calculated as a function of input frequency and the number of coactivated synapses. When few synapses were coactivated, Ca2+ influx was small, even for high-frequency activation. However, with larger numbers of coactivated synapses, there was a steep increase in Ca2+ influx with increasing input frequency because of the voltage-dependent nature of the NMDA receptor-mediated conductance. Nevertheless, total Ca2+ influx was never increased more than fourfold by increasing input frequency or the number of coactivated synapses.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Metabotropic Glutamate Receptor Antagonist AIDA Blocks Induction of Mossy Fiber-CA3 LTP In Vivo

2005 ◽  
Vol 93 (5) ◽  
pp. 2668-2673 ◽  
Author(s):  
Kenira J. Thompson ◽  
Mario L. Mata ◽  
James E. Orfila ◽  
Edwin J. Barea-Rodriguez ◽  
Joe L. Martinez
Keyword(s):  
Mossy Fiber ◽  
Long Term Potentiation ◽  
Initial Slope ◽  
Maximal Response ◽  
Excitatory Postsynaptic Potential ◽  
Sprague Dawley ◽  
Metabotropic Glutamate ◽  
Term Potentiation

Metabotropic glutamate receptors (mGluR) are implicated in long-term memory storage. mGluR-I and mGluR-II antagonists impede various forms of learning and long-term potentiation (LTP) in animals. Despite the evidence linking mGluR to learning mechanisms, their role in mossy fiber-CA3 long-term potentiation (LTP) is not yet clear. To explain the involvement of mGluR-I in memory mechanisms, we examined the function of the mGluR-I antagonist 1-aminoindan-1, 5-dicarboxylic acid (AIDA) on the induction of mossy fiber-CA3 LTP in vivo in male Sprague Dawley and Fischer 344 (F344) rats. Acute extracellular mossy fiber (MF) responses were evoked by stimulation of the MF bundle and recorded in the stratum lucidum of CA3. The excitatory postsynaptic potential (EPSP) magnitude was measured by using the initial slope of the field EPSP slope measured 2–3 ms after response onset. After collection of baseline MF-CA3 responses at 0.05 Hz, animals received either ((±))-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid ( N-methyl-d-aspartate-R antagonist, 10 mg/kg ip), naloxone (opioid-R antagonist, 10 mg/kg ip), or AIDA (mGluR antagonist, 1 mg/kg ip or 37.5 nmol ic). LTP was induced by two 100-Hz trains at the intensity sufficient to evoke 50% of the maximal response. Responses were collected for an additional 1 h. AIDA blocked induction of LTP in the mossy fiber pathway ( P < 0.05) in both strains of rats after systemic and in Sprague Dawley rats after intrahippocampal injection.

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