scholarly journals Mechanisms of Calcium Influx into Hippocampal Spines: Heterogeneity among Spines, Coincidence Detection by NMDA Receptors, and Optical Quantal Analysis

1999 ◽  
Vol 19 (6) ◽  
pp. 1976-1987 ◽  
Author(s):  
Rafael Yuste ◽  
Ania Majewska ◽  
Sydney S. Cash ◽  
Winfried Denk
Keyword(s):  
Nmda Receptors ◽  
Calcium Influx ◽  
Coincidence Detection ◽  
Quantal Analysis

scholarly journals Absence of Whisker-Related Pattern Formation in Mice with NMDA Receptors Lacking Coincidence Detection Properties and Calcium Signaling

2003 ◽  
Vol 23 (6) ◽  
pp. 2323-2332 ◽  
Author(s):  
York Rudhard ◽  
Matthias Kneussel ◽  
Mohammed A. Nassar ◽  
Georg F. Rast ◽  
Alexander J. Annala ◽  
...  
Keyword(s):  
Pattern Formation ◽  
Nmda Receptors ◽  
Calcium Signaling ◽  
Coincidence Detection ◽  
Related Pattern

NMDA receptors amplify calcium influx into dendritic spines during associative pre- and postsynaptic activation

10.1038/363 ◽  
1998 ◽  
Vol 1 (2) ◽  
pp. 114-118 ◽  
Author(s):  
Jackie Schiller ◽  
Yitzhak Schiller ◽  
David E. Clapham
Keyword(s):  
Nmda Receptors ◽  
Dendritic Spines ◽  
Calcium Influx

scholarly journals Voltage-independent GluN2A-type NMDA receptor Ca2+ signaling promotes audiogenic seizures, attentional and cognitive deficits in mice

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Ilaria Bertocchi ◽  
Ahmed Eltokhi ◽  
Andrey Rozov ◽  
Vivan Nguyễn Chi ◽  
Vidar Jensen ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Nmda Receptor ◽  
Nmda Receptors ◽  
Focal Epilepsy ◽  
Mechanistic Explanation ◽  
Audiogenic Seizures ◽  
Coincidence Detection ◽  
Oscillatory Activity ◽  
Sensory Stimuli ◽  
Inherent Voltage

AbstractThe NMDA receptor-mediated Ca2+ signaling during simultaneous pre- and postsynaptic activity is critically involved in synaptic plasticity and thus has a key role in the nervous system. In GRIN2-variant patients alterations of this coincidence detection provoked complex clinical phenotypes, ranging from reduced muscle strength to epileptic seizures and intellectual disability. By using our gene-targeted mouse line (Grin2aN615S), we show that voltage-independent glutamate-gated signaling of GluN2A-containing NMDA receptors is associated with NMDAR-dependent audiogenic seizures due to hyperexcitable midbrain circuits. In contrast, the NMDAR antagonist MK-801-induced c-Fos expression is reduced in the hippocampus. Likewise, the synchronization of theta- and gamma oscillatory activity is lowered during exploration, demonstrating reduced hippocampal activity. This is associated with exploratory hyperactivity and aberrantly increased and dysregulated levels of attention that can interfere with associative learning, in particular when relevant cues and reward outcomes are disconnected in space and time. Together, our findings provide (i) experimental evidence that the inherent voltage-dependent Ca2+ signaling of NMDA receptors is essential for maintaining appropriate responses to sensory stimuli and (ii) a mechanistic explanation for the neurological manifestations seen in the NMDAR-related human disorders with GRIN2 variant-meidiated intellectual disability and focal epilepsy.

scholarly journals Dysregulation of erythropoiesis and altered erythroblastic NMDA receptor-mediated calcium influx in Lrfn2-deficient mice

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245624
Author(s):  
Ryuta Maekawa ◽  
Hideki Muto ◽  
Minoru Hatayama ◽  
Jun Aruga
Keyword(s):  
Bone Marrow ◽  
Nmda Receptor ◽  
Nmda Receptors ◽  
Bone Marrow Cells ◽  
Calcium Influx ◽  
Marrow Cell ◽  
Nmda Receptor Antagonist ◽  
Receptor Expression ◽  
Nmda Receptor Function ◽  
Marrow Cells

LRFN2 encodes a synaptic adhesion-like molecule that physically interacts with N-methyl-D-aspartate (NMDA) receptor 1 and its scaffold proteins. Previous studies in humans and mice have demonstrated its genetic association with neurodevelopmental disorders such as learning deficiency and autism. In this study, we showed that Lrfn2-deficient (KO) mice exhibit abnormalities of erythropoietic systems due to altered NMDA receptor function. In mature Lrfn2 KO male mice, peripheral blood tests showed multilineage abnormalities, including normocytic erythrocythemia, and reduced platelet volume. Colony forming unit assay using bone marrow cells revealed decreases in the counts of erythrocyte progenitors (CFU-E) as well as granulocytes and monocyte progenitors (CFU-GM). Whole bone marrow cell staining showed that serum erythropoietin (EPO) level was decreased and EPO receptor-like immunoreactivity was increased. Flow cytometry analysis of bone marrow cells revealed increased early erythroblast count and increased transferrin receptor expression in late erythroblasts. Further, we found that late erythroblasts in Lrfn2 KO exhibited defective NMDA receptor-mediated calcium influx, which was inhibited by the NMDA receptor antagonist MK801. These results indicate that Lrfn2 has biphasic roles in hematopoiesis and is associated with the functional integrity of NMDA receptors in hematopoietic cells. Furthermore, taken together with previous studies that showed the involvement of NMDA receptors in hematopoiesis, the results of this study indicate that Lrfn2 may regulate erythropoiesis through its regulatory activity on NMDA receptors.

scholarly journals Tonic Activation of Extrasynaptic NMDA Receptors Decreases Intrinsic Excitability and Promotes Bistability in a Model of Neuronal Activity

2019 ◽  
Vol 21 (1) ◽  
pp. 206
Author(s):  
David Gall ◽  
Geneviève Dupont
Keyword(s):  
Potassium Channels ◽  
Electrical Activity ◽  
Nmda Receptors ◽  
Neuronal Activity ◽  
Neuronal Excitability ◽  
Calcium Influx ◽  
Tonic Activity ◽  
Stimulus Interval ◽  
Simple Description ◽  
Calcium Activated Potassium Channels

NMDA receptors (NMDA-R) typically contribute to excitatory synaptic transmission in the central nervous system. While calcium influx through NMDA-R plays a critical role in synaptic plasticity, experimental evidence indicates that NMDAR-mediated calcium influx also modifies neuronal excitability through the activation of calcium-activated potassium channels. This mechanism has not yet been studied theoretically. Our theoretical model provides a simple description of neuronal electrical activity that takes into account the tonic activity of extrasynaptic NMDA receptors and a cytosolic calcium compartment. We show that calcium influx mediated by the tonic activity of NMDA-R can be coupled directly to the activation of calcium-activated potassium channels, resulting in an overall inhibitory effect on neuronal excitability. Furthermore, the presence of tonic NMDA-R activity promotes bistability in electrical activity by dramatically increasing the stimulus interval where both a stable steady state and repetitive firing can coexist. These results could provide an intrinsic mechanism for the constitution of memory traces in neuronal circuits. They also shed light on the way by which β -amyloids can alter neuronal activity when interfering with NMDA-R in Alzheimer’s disease and cerebral ischemia.

scholarly journals Calcium Influx through NMDA Receptors Directly Evokes GABA Release in Olfactory Bulb Granule Cells

2000 ◽  
Vol 20 (13) ◽  
pp. 5124-5134 ◽  
Author(s):  
Brian Halabisky ◽  
Daniel Friedman ◽  
Milan Radojicic ◽  
Ben W. Strowbridge
Keyword(s):  
Olfactory Bulb ◽  
Nmda Receptors ◽  
Granule Cells ◽  
Calcium Influx ◽  
Gaba Release

Mechanism linking NMDA receptor activation to modulation of voltage-gated sodium current in distal retina

2003 ◽  
Vol 284 (5) ◽  
pp. C1193-C1204 ◽  
Author(s):  
Scott F. Davis ◽  
Cindy L. Linn
Keyword(s):  
Sodium Channel ◽  
Nmda Receptors ◽  
Sodium Channels ◽  
Calcium Influx ◽  
Receptor Activation ◽  
Horizontal Cells ◽  
Channel Modulation ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Nmda Channels

In this study, we investigated the mechanism that links activation of N-methyl-D-aspartate (NMDA) receptors to inhibition of voltage-gated sodium channels in isolated catfish cone horizontal cells. NMDA channels were activated in voltage-clamped cells incubated in low-calcium saline or dialyzed with the calcium chelator BAPTA to determine that calcium influx through NMDA channels is required for sodium channel modulation. To determine whether calcium influx through NMDA channels triggers calcium-induced calcium release (CICR), cells were loaded with the calcium-sensitive dye calcium green 2 and changes in relative fluorescence were measured in response to NMDA. Responses were compared with measurements obtained when caffeine depleted stores. Voltage-clamp studies demonstrated that CICR modulated sodium channels in a manner similar to that of NMDA. Blocking NMDA receptors with AP-7, blocking CICR with ruthenium red, depleting stores with caffeine, or dialyzing cells with calmodulin antagonists W-5 or peptide 290–309 all prevented sodium channel modulation. These results support the hypothesis that NMDA modulation of voltage-gated sodium channels in horizontal cells requires CICR and activation of a calmodulin-dependent signaling pathway.

Amplification of calcium signals at dendritic spines provides a method for CNS quantal analysis

1999 ◽  
Vol 77 (9) ◽  
pp. 651-659 ◽  
Author(s):  
Sabrina Wang ◽  
Oliver Prange ◽  
Timothy H Murphy
Keyword(s):  
Synaptic Transmission ◽  
Nmda Receptors ◽  
Dendritic Spines ◽  
Small Volume ◽  
Synaptic Activity ◽  
Significant Elevation ◽  
Calcium Signals ◽  
High Affinity ◽  
Quantal Analysis ◽  
Intracellular Ca

It has been proposed that the small volume of a dendritic spine can amplify Ca2+ signals during synaptic transmission. Accordingly, we have performed calculations to determine whether the activation of N-methyl-D-aspartate (NMDA) type glutamate receptors during synaptic transmission results in significant elevation in intracellular Ca2+ levels, permitting optical detection of synaptic signals within a single spine. Simple calculations suggest that the opening of even a single NMDA receptor would result in the influx of ~ 310 000 Ca2+ ions into the small volume of a spine, producing changes in Ca2+ levels that are readily detectable using high affinity Ca2+ indicators such as fura-2 or fluo-3. Using fluorescent Ca2+ indicators, we have imaged local Ca2+ transients mediated by NMDA receptors in spines and dendritic shafts attributed to spontaneous miniature synaptic activity. Detailed analysis of these quantal events suggests that the current triggering these transients is attributed to the activation of <10 NMDA receptors. The frequency of these miniature synaptic Ca2+ transients is not randomly distributed across synapses, as some synapses can display a >10-fold higher frequency of transients than others. As expected for events mediated by NMDA receptors, miniature synaptic Ca2+ transients were suppressed by extracellular Mg2+ at negative membrane potentials; however, the Mg2+ block could be removed by depolarization.Key words: miniature release, N-methyl-D-aspartate (NMDA), calcium, glutamate, spine.

scholarly journals Blockade of NR2A-Containing NMDA Receptors Induces Tau Phosphorylation in Rat Hippocampal Slices

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Julie Allyson ◽  
Eve Dontigny ◽  
Yves Auberson ◽  
Michel Cyr ◽  
Guy Massicotte
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Cell Function ◽  
Calcium Influx ◽  
Hippocampal Slices ◽  
Neuronal Cell ◽  
Tau Phosphorylation ◽  
Tau Proteins ◽  
Rich Domain ◽  
Neuronal Membranes

Physiological activation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors has been proposed to play a key role in both neuronal cell function and dysfunction. In the present study, we used selective NMDA receptor antagonists to investigate the involvement of NR2A and NR2B subunits in the modulatory effect of basal NMDA receptor activity on the phosphorylation of Tau proteins. We observed, in acute hippocampal slice preparations, that blockade of NR2A-containing NMDA receptors by the NR2A antagonist NVP-AAM077 provoked the hyperphosphorylation of a residue located in the proline-rich domain of Tau (i.e., Ser199). This effect seemed to be Ser199 specific as there was no increase in phosphorylation at Ser262 and Ser409 residues located in the microtubule-binding and C-terminal domains of Tau proteins, respectively. From a mechanistic perspective, our study revealed that blockade of NR2A-containing receptors influences Tau phosphorylation probably by increasing calcium influx into neurons, which seems to rely on accumulation of new NR1/NR2B receptors in neuronal membranes and could involve the cyclin-dependent kinase 5 pathway.

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