NMDA receptors at excitatory synapses in the hippocampus: test of a theory of magnesium block

1993 ◽  
Vol 156 (1-2) ◽  
pp. 73-77 ◽  
Author(s):  
John M. Bekkers ◽  
Charles F. Stevens
Keyword(s):  
Nmda Receptors ◽  
Excitatory Synapses ◽  
Magnesium Block

Short-Term Potentiation of Miniature Excitatory Synaptic Currents Causes Excitation of Supraoptic Neurons

2000 ◽  
Vol 83 (5) ◽  
pp. 2542-2553 ◽  
Author(s):  
Samuel B. Kombian ◽  
Michiru Hirasawa ◽  
Didier Mouginot ◽  
Xihua Chen ◽  
Quentin J. Pittman
Keyword(s):  
Nmda Receptors ◽  
Postsynaptic Membrane ◽  
High Frequency Stimulation ◽  
Excitatory Synapses ◽  
Short Term ◽  
Cell Excitability ◽  
Term Potentiation ◽  
Before And After ◽  
Frequency Stimulation ◽  
Supraoptic Neurons

Magnocellular neurons (MCNs) of the hypothalamic supraoptic nucleus (SON) secrete vasopressin and oxytocin. With the use of whole-cell and nystatin-perforated patch recordings of MCNs in current- and voltage-clamp modes, we show that high-frequency stimulation (HFS, 10–200 Hz) of excitatory afferents induces increases in the frequency and amplitude of 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo(f)quinoxaline-7-sulfonamide (NBQX)-sensitive miniature excitatory postsynaptic currents (mEPSCs) lasting up to 20 min. This synaptic enhancement, referred to as short-term potentiation (STP), could be induced repeatedly; required tetrodotoxin (TTX)-dependent action potentials to initiate, but not to maintain; and was independent of postsynaptic membrane potential, N-methyl-d-aspartate (NMDA) receptors, or retrograde neurohypophyseal neuropeptide release. STP was not accompanied by changes in the conductance of the MCNs or in the responsiveness of the postsynaptic non-NMDA receptors, as revealed by brief application of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate. mEPSCs showed similar rise times before and after HFS and analysis of amplitude distributions of mEPSCs revealed one or more peaks pre-HFS and the appearance of additional peaks post-HFS, which were equidistant from the first peak. STP of mEPSCs was not associated with enhanced evoked responses, but was associated with an NBQX-sensitive increase in spontaneous activity of MCNs. Thus we have identified a particularly long-lasting potentiation of excitatory synapses in the SON, which has a presynaptic locus, is dissociated from changes in evoked release, and which regulates postsynaptic cell excitability.

scholarly journals IQSEC2-Associated Intellectual Disability and Autism

2019 ◽  
Vol 20 (12) ◽  
pp. 3038 ◽  
Author(s):  
Nina S. Levy ◽  
George K. E. Umanah ◽  
Eli J. Rogers ◽  
Reem Jada ◽  
Orit Lache ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Nmda Receptors ◽  
Glutamate Receptors ◽  
Ampa Receptor ◽  
Ampa Receptors ◽  
Neuronal Development ◽  
Catalytic Domain ◽  
Excitatory Synapses ◽  
Ampa Receptor Subunit ◽  
Ion Influx

Mutations in IQSEC2 cause intellectual disability (ID), which is often accompanied by seizures and autism. A number of studies have shown that IQSEC2 is an abundant protein in excitatory synapses and plays an important role in neuronal development as well as synaptic plasticity. Here, we review neuronal IQSEC2 signaling with emphasis on those aspects likely to be involved in autism. IQSEC2 is normally bound to N-methyl-D-aspartate (NMDA)-type glutamate receptors via post synaptic density protein 95 (PSD-95). Activation of NMDA receptors results in calcium ion influx and binding to calmodulin present on the IQSEC2 IQ domain. Calcium/calmodulin induces a conformational change in IQSEC2 leading to activation of the SEC7 catalytic domain. GTP is exchanged for GDP on ADP ribosylation factor 6 (ARF6). Activated ARF6 promotes downregulation of surface α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors through a c-jun N terminal kinase (JNK)-mediated pathway. NMDA receptors, AMPA receptors, and PSD-95 are all known to be adversely affected in autism. An IQSEC2 transgenic mouse carrying a constitutively active mutation (A350V) shows autistic features and reduced levels of surface AMPA receptor subunit GluA2. Sec7 activity and AMPA receptor recycling are presented as two targets, which may respond to drug treatment in IQSEC2-associated ID and autism.

The mechanism of magnesium block of NMDA receptors

1994 ◽  
Vol 6 (2) ◽  
pp. 87-96 ◽  
Author(s):  
J.Peter Ruppersberg ◽  
Eberhard v. Kitzing ◽  
Ralf Schoepfer
Keyword(s):  
Nmda Receptors ◽  
Magnesium Block

Glycine Uptake Governs Glycine Site Occupancy at NMDA Receptors of Excitatory Synapses

1998 ◽  
Vol 80 (6) ◽  
pp. 3336-3340 ◽  
Author(s):  
Albert J. Berger ◽  
Stéphane Dieudonné ◽  
Philippe Ascher
Keyword(s):  
Nmda Receptors ◽  
Binding Sites ◽  
Site Occupancy ◽  
Neonatal Rat ◽  
Excitatory Synapses ◽  
Glycine Site ◽  
Isolated Cells ◽  
Apparent Dissociation Constant ◽  
Glycine Uptake ◽  
Glycine Concentration

Berger, Albert J., Stéphane Dieudonné, and Philippe Ascher. Glycine uptake governs glycine site occupancy at NMDA receptors of excitatory synapses. J. Neurophysiol. 80: 3336–3340, 1998. At central synapses occupation of glycine binding sites of N-methyl-d-aspartate receptors (NMDA-Rs) is a necessary prerequisite for the excitatory neurotransmitter glutamate to activate these receptors. There is conflicting evidence as to whether glycine binding sites normally are saturated. If they are not, then alterations in local glycine concentration could modulate excitatory synaptic transmission. By using an in vitro brain stem slice preparation we investigated whether the glycine site is saturated for synaptically activated NMDA-Rs in neonatal rat hypoglossal motoneurons. We found that the NMDA-R–mediated component of spontaneous miniature excitatory postsynaptic currents could be potentiated by exogenously applied glycine as well as by d-serine. The effects of glycine were observed only at concentrations (100 μM or more) two orders of magnitude above the apparent dissociation constant of glycine from NMDA receptors. In contrast, d-serine, a nontransported NMDA-R glycine site agonist, was effective in the low micromolar range, i.e., at concentrations similar to those found to be effective on isolated cells or on outside-out patches. We conclude that at these synapses the glycine concentration around synaptic NMDA-Rs is set below the concentration required to saturate their glycine site and is likely to be stabilized by a powerful glycine transport mechanism.

NMDA and non-NMDA receptors are co-localized at individual excitatory synapses in cultured rat hippocampus

Nature ◽  
1989 ◽  
Vol 341 (6239) ◽  
pp. 230-233 ◽  
Author(s):  
John M. Bekkers ◽  
Charles F. Stevens
Keyword(s):  
Nmda Receptors ◽  
Rat Hippocampus ◽  
Excitatory Synapses

NMDA and non-NMDA receptors are co-localized at excitatory synapses of rat hypoglossal motoneurons

1997 ◽  
Vol 227 (1) ◽  
pp. 5-8 ◽  
Author(s):  
Jennifer A O'Brien ◽  
Jeffry S Isaacson ◽  
Albert J Berger
Keyword(s):  
Nmda Receptors ◽  
Excitatory Synapses ◽  
Hypoglossal Motoneurons

Early events in the trafficking of N-methyl-d-aspartate (NMDA) receptors

2003 ◽  
Vol 31 (4) ◽  
pp. 885-888 ◽  
Author(s):  
R.J. Wenthold ◽  
N. Sans ◽  
S. Standley ◽  
K. Prybylowski ◽  
R.S. Petralia
Keyword(s):  
Endoplasmic Reticulum ◽  
Synaptic Plasticity ◽  
Nmda Receptor ◽  
Nmda Receptors ◽  
Biosynthetic Pathway ◽  
Biological Properties ◽  
Receptor Trafficking ◽  
Excitatory Synapses ◽  
Multiple Functions ◽  
Subunit Assembly

The N-methyl-d-aspartate (NMDA) receptor plays a central role at excitatory synapses where it has been implicated in multiple functions associated with synaptic plasticity. While this receptor has been intensely studied with respect to its physiology and pharmacology, its cell-biological properties, such as subunit assembly, post-translational processing and trafficking in neurons, are only beginning to be addressed. Critical to many of the functions of the NMDA receptor are the multiple proteins with which it interacts. While these interactions have been most thoroughly studied with respect to the receptor at the synapse, the same proteins may also interact with the receptor much earlier in its biosynthetic pathway and play important roles in receptor trafficking from the endoplasmic reticulum to the synapse.

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