An Ibotenate-Selective Metabotropic Glutamate Receptor: Mediates Protein Phosphorylation in Cultured Hippocampal Pyramidal Neurons

2008 ◽  
Vol 62 (5) ◽  
pp. 1764-1772 ◽  
Author(s):  
W. K. Scholz
Keyword(s):  
Protein Phosphorylation ◽  
Glutamate Receptor ◽  
Pyramidal Neurons ◽  
Metabotropic Glutamate Receptor ◽  
Hippocampal Pyramidal Neurons ◽  
Metabotropic Glutamate

scholarly journals Prenatal treatment with rapamycin restores enhanced hippocampal mGluR-LTD and mushroom spine size in a Down’s syndrome mouse model

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jesús David Urbano-Gámez ◽  
Juan José Casañas ◽  
Itziar Benito ◽  
María Luz Montesinos
Keyword(s):  
Intellectual Disability ◽  
Pyramidal Neurons ◽  
Metabotropic Glutamate Receptor ◽  
Therapeutic Potential ◽  
Mammalian Target Of Rapamycin ◽  
Memory Deficits ◽  
Prenatal Treatment ◽  
Hippocampal Pyramidal Neurons ◽  
Metabotropic Glutamate ◽  
Mushroom Spines

AbstractDown syndrome (DS) is the most frequent genetic cause of intellectual disability including hippocampal-dependent memory deficits. We have previously reported hippocampal mTOR (mammalian target of rapamycin) hyperactivation, and related plasticity as well as memory deficits in Ts1Cje mice, a DS experimental model. Here we characterize the proteome of hippocampal synaptoneurosomes (SNs) from these mice, and found a predicted alteration of synaptic plasticity pathways, including long term depression (LTD). Accordingly, mGluR-LTD (metabotropic Glutamate Receptor-LTD) is enhanced in the hippocampus of Ts1Cje mice and this is correlated with an increased proportion of a particular category of mushroom spines in hippocampal pyramidal neurons. Remarkably, prenatal treatment of these mice with rapamycin has a positive pharmacological effect on both phenotypes, supporting the therapeutic potential of rapamycin/rapalogs for DS intellectual disability.

Metabotropic glutamate receptor-mediated suppression of L-type calcium current in acutely isolated neocortical neurons

1992 ◽  
Vol 68 (3) ◽  
pp. 833-842 ◽  
Author(s):  
R. J. Sayer ◽  
P. C. Schwindt ◽  
W. E. Crill
Keyword(s):  
Glutamate Receptor ◽  
Pyramidal Neurons ◽  
Metabotropic Glutamate Receptor ◽  
High Threshold ◽  
External Application ◽  
Metabotropic Glutamate ◽  
Neocortical Neurons ◽  
Old Rats ◽  
Low Threshold ◽  
Ca2 Channels

1. The effects of metabotropic glutamate receptor (mGluR) stimulation on whole-cell Ca2+ currents were studied in pyramidal neurons isolated from the dorsal frontoparietal neocortex of rat. The selective mGluR agonist cis-(+/-)-1-aminocyclopentane-1,3-dicarboxylic acid [trans-ACPD (100 microM)] suppressed the peak high-threshold Ca2+ current by 21 +/- 1.7% (mean +/- SE) in 40 of 43 cells from 10- to 21-day-old rats. Consistent with previous findings for mGluR, glutamate, quisqualate, and ibotenate [but not alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)] reduced the Ca2+ currents, and the responses were not blocked by the ionotropic glutamate receptor antagonists 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) and DL-2-amino-5-phosphonovaleric acid (APV). EC50S for Ca2+ current suppression were 29 nM for quisqualate, 2.3 microM for glutamate, and 13 microM for trans-ACPD. 2. The low-threshold Ca2+ current was not modulated by trans-ACPD. The component of the high-threshold CA2+ current suppressed by mGluR was determined by pharmacology; the responses were not affected by omega-conotoxin GVIA but were occluded by the dihydropyridine Ca2+ antagonist nifedipine. Ca2+ tail currents prolonged by the dihydropyridine Ca2+ agonist (+)-SDZ 202-79] were suppressed by mGluR stimulation in parallel with the peak current. These findings strongly suggest that L-type Ca2+ channels are modulated by mGluR. 3. In neurons dialyzed with 100 microM guanosine 5'-(gamma-thio)triphosphate (GTP-gamma-S), Ca2+ current suppression was elicited by the first application of trans-ACPD (in 5 of 6 cells), but not by subsequent applications. Responses in neurons dialyzed with 2 mM guanosine 5'-(beta-thio)diphosphate (GDP-beta-S) were significantly smaller than controls. The results are consistent with mGluR acting via linkage to a G protein. 4. The responses to mGluR agonists were smaller when the external Ca2+ was replaced by Ba2+, indicating that some part of the mechanism underlying the current suppression is Ca2+ dependent. Because mGluR stimulates phosphoinositide turnover and release of Ca2+ from intracellular stores in other types of neurons, the possibility of released Ca2+ mediating inactivation of Ca2+ channels was considered. However, the Ca2+ current suppression was not attenuated by strong intracellular Ca2+ buffering [20 mM bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA)], by dialysis with 100 microM inositol-1,4,5-triphosphate (IP3), or by external application of 1 microM thapsigargin. 5. We conclude that in neocortical neurons, one action of mGluR is to suppress the component of high-threshold Ca2+ current conducted by L-type Ca2+ channels.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Experience-Induced Arc/Arg3.1 Primes CA1 Pyramidal Neurons for Metabotropic Glutamate Receptor-Dependent Long-Term Synaptic Depression

Neuron ◽  
2013 ◽  
Vol 80 (1) ◽  
pp. 72-79 ◽  
Author(s):  
Vikram Jakkamsetti ◽  
Nien-Pei Tsai ◽  
Christina Gross ◽  
Gemma Molinaro ◽  
Katie A. Collins ◽  
...  
Keyword(s):  
Glutamate Receptor ◽  
Pyramidal Neurons ◽  
Metabotropic Glutamate Receptor ◽  
Synaptic Depression ◽  
Metabotropic Glutamate ◽  
Ca1 Pyramidal Neurons

Properties and ionic mechanisms of a metabotropic glutamate receptor-mediated slow afterdepolarization in neocortical neurons

1994 ◽  
Vol 72 (2) ◽  
pp. 693-704 ◽  
Author(s):  
C. C. Greene ◽  
P. C. Schwindt ◽  
W. E. Crill
Keyword(s):  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptors ◽  
Pyramidal Neurons ◽  
Metabotropic Glutamate Receptor ◽  
Equilibrium Potential ◽  
Cholinergic Antagonists ◽  
Recording Electrode ◽  
Metabotropic Glutamate ◽  
Ionic Mechanisms ◽  
Layer V

1. Pyramidal neurons from layer V of rat neocortex were recorded intracellularly in a brain slice preparation to study their response to stimulation of metabotropic glutamate receptors (mGluRs) by bath application of the selective mGluR agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) and by the nonselective agonists glutamate and quisqualate. 2. The principal postsynaptic effect of mGluR stimulation in the presence of ionotropic glutaminergic and muscarinic cholinergic antagonists was the appearance of a slow afterdepolarization (ADP) after evoked spikes. Only an afterhyperpolarization (AHP) was present in control perfusate. After 20 spikes evoked individually at 100 Hz the ADP peaked at 317 +/- 117 (SD) ms after the spike train, ranged from 1 to 12 mV in peak amplitude, and decayed over 7.4 +/- 4.7 s. This effect was not blocked by L-2-amino-3-phosphono-propionic acid (1 mM). Spikes evoked in the presence of the ionotropic glutamate receptor agonist R,S-alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) did not have an ADP. 3. A detectable ADP appeared at concentrations of 0.1 microM quisqualate or 0.5 microM 1S,3R-ACPD. Maximum ADP amplitude was obtained with 5 microM quisqualate or 100 microM 1S,3R-ACPD. The ADP appeared after a single evoked spike in most cells tested and ADP amplitude increased to a maximum as the number of spikes evoked at 100 Hz was increased to between 5 and 20. 4. The ionic mechanisms underlying the ADP were examined by ion substitution and the application of channel-blocking agents. No difference in ADP amplitude was observed when the recording electrode contained CH3SO4. instead of Cl.. The ADP was present after 3 mM extracellular Cs+ were added to block the hyperpolarization-activated cation current or when 100 microM Ba2+ were included to block voltage-gated K+ currents. The ADP was abolished when Mn2+ was substituted for Ca2+ in the perfusate or when the Ca2+ chelator 5,5'-dimethyl-bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid was included in the recording electrode. A large ADP followed Ca2+ spikes evoked in the presence of 1 microM tetrodotoxin with 20 mM tetraethylammonium in the perfusate or with Cs+ substituted for K+ in the recording electrode. The amplitude of the ADP after the Ca2+ spikes was reduced by 49% when extracellular Na+ concentration was reduced from 136 to 26 mM. 5. The voltage dependence of the ADP was examined in relation to K+ equilibrium potential (EK).(ABSTRACT TRUNCATED AT 400 WORDS)

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