Long-term NMDA receptor inhibition affects NMDA receptor expression and alters glutamatergic activity in developing rat hippocampal neurons

Toxicology ◽  
2015 ◽  
Vol 333 ◽  
pp. 147-155 ◽  
Author(s):  
Barbara Sinner ◽  
Oliver Friedrich ◽  
Regina Lindner ◽  
Anika Bundscherer ◽  
Bernhard M. Graf
Keyword(s):  
Nmda Receptor ◽  
Hippocampal Neurons ◽  
Receptor Expression ◽  
Receptor Inhibition ◽  
Developing Rat

Anoxia-induced LTP of isolated NMDA receptor-mediated synaptic responses

1993 ◽  
Vol 69 (5) ◽  
pp. 1774-1778 ◽  
Author(s):  
V. Crepel ◽  
C. Hammond ◽  
K. Krnjevic ◽  
P. Chinestra ◽  
Y. Ben-Ari
Keyword(s):  
Nmda Receptor ◽  
Neuronal Death ◽  
Hippocampal Neurons ◽  
Input Resistance ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
Bath Application ◽  
Synaptic Responses

1. The effects of an anoxic-aglycemic episode (1-3 min) on the pharmacologically isolated N-methyl-D-aspartate (NMDA)-mediated responses were examined in CA1 pyramidal hippocampal neurons in vitro. 2. An anoxic-aglycemic episode induced a long term potentiation (LTP) of the NMDA receptor-mediated field excitatory post-synoptic potentials (EPSPs). This LTP, referred to as anoxic LTP, was observed in the presence of 1) a normal Mg2+ concentration [+40.1 +/- 5% (mean +/- SE)], 2) a low Mg2+ concentration (+52.2 +/- 10%), or 3) a Mg2+ free (+49 +/- 11%), 1 h after anoxia. 3. Bath application of D-2-amino-5-phosphonovaleric acid (D-APV, 20 microM, 15-21 min) before, during, and after the anoxic-aglycemic episode, which transiently blocked the synaptic NMDA receptor mediated response, prevented the induction of anoxic LTP. 4. The intracellularly recorded NMDA receptor-mediated EPSP was also persistently potentiated by anoxia-aglycemia (+47 +/- 4%). This potentiation was not associated with changes in membrane potential or input resistance. 5. These findings provide the first evidence that an anoxic-aglycemic episode induces an LTP of NMDA receptor-mediated responses. This potentiation may participate in the cascade of events that lead to delayed neuronal death.

Pilocapine alters NMDA receptor expression and function in hippocampal neurons: NADPH oxidase and ERK1/2 mechanisms

2011 ◽  
Vol 42 (3) ◽  
pp. 482-495 ◽  
Author(s):  
Roberto Di Maio ◽  
Pier G. Mastroberardino ◽  
Xiaoping Hu ◽  
Laura Montero ◽  
J. Timothy Greenamyre
Keyword(s):  
Nmda Receptor ◽  
Nadph Oxidase ◽  
Hippocampal Neurons ◽  
Receptor Expression ◽  
And Function

scholarly journals Septin 9 interacts with kinesin KIF17 and interferes with the mechanism of NMDA receptor cargo binding and transport

2016 ◽  
Vol 27 (6) ◽  
pp. 897-906 ◽  
Author(s):  
Xiaobo Bai ◽  
Eva P. Karasmanis ◽  
Elias T. Spiliotis
Keyword(s):  
Nmda Receptor ◽  
Hippocampal Neurons ◽  
Intracellular Transport ◽  
Tail Domain ◽  
Septin 9 ◽  
Microtubule Motor ◽  
Underlying Mechanisms ◽  
Dependent Transport ◽  
Developing Rat ◽  
Cargo Binding

Intracellular transport involves the regulation of microtubule motor interactions with cargo, but the underlying mechanisms are not well understood. Septins are membrane- and microtubule-binding proteins that assemble into filamentous, scaffold-like structures. Septins are implicated in microtubule-dependent transport, but their roles are unknown. Here we describe a novel interaction between KIF17, a kinesin 2 family motor, and septin 9 (SEPT9). We show that SEPT9 associates directly with the C-terminal tail of KIF17 and interacts preferentially with the extended cargo-binding conformation of KIF17. In developing rat hippocampal neurons, SEPT9 partially colocalizes and comigrates with KIF17. We show that SEPT9 interacts with the KIF17 tail domain that associates with mLin-10/Mint1, a cargo adaptor/scaffold protein, which underlies the mechanism of KIF17 binding to the NMDA receptor subunit 2B (NR2B). Significantly, SEPT9 interferes with binding of the PDZ1 domain of mLin-10/Mint1 to KIF17 and thereby down-regulates NR2B transport into the dendrites of hippocampal neurons. Measurements of KIF17 motility in live neurons show that SEPT9 does not affect the microtubule-dependent motility of KIF17. These results provide the first evidence of an interaction between septins and a nonmitotic kinesin and suggest that SEPT9 modulates the interactions of KIF17 with membrane cargo.

Anoxic LTP is mediated by the redox modulatory site of the NMDA receptor

1994 ◽  
Vol 72 (6) ◽  
pp. 3017-3022 ◽  
Author(s):  
H. Gozlan ◽  
D. Diabira ◽  
P. Chinestra ◽  
Y. Ben-Ari
Keyword(s):  
Nmda Receptor ◽  
Hippocampal Neurons ◽  
Field Potential ◽  
Extracellular Recording ◽  
Glucose Deprivation ◽  
Long Term Potentiation ◽  
Receptor Field ◽  
Oxygen And Glucose Deprivation ◽  
Term Potentiation

1. The effects of redox reagents, 5,5'-dithiobis-2-nitrobenzoic acid (DTNB) and tris(carboxyethyl)phosphine (TCEP), on anoxia-induced long-term potentiation (LTP) were investigated in CA1 hippocampal neurons using extracellular recording techniques. Experiments were performed in the presence of 0.1 mM MgCl2 and 10 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) to pharmacologically isolate N-methyl-D-aspartate (NMDA) receptor-mediated responses. 2. DTNB (200 microM), a thiol oxidizing reagent, reduces by 52 +/- 9% (mean +/- SE) (n = 9/9) NMDA-receptor field potentials evoked by electrical stimulation of Schaffer collaterals and this effect could not be reversed by extensive washing. Nearly the same reduction of the initial response was obtained with different concentrations of DTNB (100 and 500 microM), but the time required to reach the maximal inhibition was concentration-dependent. 3. In keeping with an earlier study oxygen and glucose deprivation for 2-3 min induced a long-term potentiation (LTP) of the NMDA receptor response (+65 +/- 16%, n = 4/6). This potentiation was reversed by DTNB (100-500 microM) (-47 +/- 18%; n = 4/4) and the initial LTP could not be restored upon extensive washing of the drug. 4. TCEP (200 microM), a reagent which reduces S-S bond, amplified the electrically evoked NMDA-receptor EPSP (+27 +/- 12%; n = 3). In addition, TCEP (200 microM), nearly completely reversed the effect of DTNB (200 microM) on anoxia-induced LTP (+56 +/- 19%; n = 3/3). Preliminary results also indicate that TCEP occlude anoxic-LTP (n = 3/4). 5. Following DTNB (200 microM) treatment, oxygen and glucose deprivation did not generate anoxic LTP and extensive washing did not restore a potentiated NMDA field potential. 6. These observations strongly suggest that the redox site of the NMDA receptor is involved in the induction and the maintenance of the anoxic LTP of the NMDA receptor-mediated response in CA1.

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.

scholarly journals Sensitivity of Synaptic Plasticity to the Ca2+ Permeability of NMDA Channels: A Model of Long-Term Potentiation in Hippocampal Neurons

1993 ◽  
Vol 5 (5) ◽  
pp. 681-694 ◽  
Author(s):  
Erik De Schutter ◽  
James M. Bower
Keyword(s):  
Nmda Receptor ◽  
Dendritic Spines ◽  
Hippocampal Neurons ◽  
Dendritic Tree ◽  
Long Term Potentiation ◽  
Synaptic Activation ◽  
Term Potentiation ◽  
Nmda Channels ◽  
Maximum Amplification

We have examined a model by Holmes and Levy (1990) of the induction of associative long-term potentiation (LTP) by a rise in the free Ca2+ concentration ([Ca2+]) after synaptic activation of dendritic spines. The previously reported amplification of the change in [Ca2+] caused by coactivation of several synapses was found to be quite sensitive to changes in the permeability of the N-methyl-D-aspartate (NMDA) receptor channels to Ca2+. Varying this parameter indicated that maximum amplification is obtained at values that are close to Ca2+ permeabilities reported in the literature. However, amplification failed if permeability is reduced by more than 50%. We also found that the maximum free [Ca2+] reached in an individual spine during synaptic coactivation of several spines depended on the location of that spine on the dendritic tree. Distal spines attained a higher [Ca2+] than proximal ones, with differences of up to 80%. The implications of this result for the uniformity of induction of associative LTP in spines in different regions of the dendrite are discussed.

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