Dimethyl Sulfoxide Suppresses NMDA- and AMPA-Induced Ion Currents and Calcium Influx and Protects against Excitotoxic Death in Hippocampal Neurons

2001 ◽  
Vol 170 (1) ◽  
pp. 180-185 ◽  
Author(s):  
Chengbiao Lu ◽  
Mark P. Mattson
Keyword(s):  
Dimethyl Sulfoxide ◽  
Hippocampal Neurons ◽  
Calcium Influx ◽  
Ion Currents

Humanin peptides block calcium influx of rat hippocampal neurons by altering fibrogenesis of Aβ1–40

Peptides ◽  
2003 ◽  
Vol 24 (5) ◽  
pp. 679-685 ◽  
Author(s):  
Ping Zou ◽  
Yanan Ding ◽  
Yinlin Sha ◽  
Baihe Hu ◽  
Songqing Nie
Keyword(s):  
Hippocampal Neurons ◽  
Calcium Influx

scholarly journals Cross talk between synaptic receptors mediates NMDA-induced suppression of inhibition

2012 ◽  
Vol 107 (9) ◽  
pp. 2532-2540 ◽  
Author(s):  
Mariangela Chisari ◽  
Charles F. Zorumski ◽  
Steven Mennerick
Keyword(s):  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Calcium Influx ◽  
Past Research ◽  
Synaptic Activation ◽  
Decay Kinetics ◽  
Nmdar Activation ◽  
Synaptic Receptors ◽  
Precise Moment ◽  
Nmdar Subunits

Past research has shown that calcium influx through NMDA receptors (NMDARs) depresses GABAA currents. We examined upstream triggers of this suppression, including involvement of target synaptic GABAA receptors and the NMDARs triggering suppression. In hippocampal neurons, conditioning with 20 μM NMDA for 20 s caused 50% suppression of GABA responses. The suppression was delayed by ∼60 s following NMDA application and persisted for at least 5 min following conditioning. Pharmacology experiments suggested a shift in both the sensitivity to GABA and a loss of functional receptors. NMDA conditioning strongly suppressed inhibitory postsynaptic currents and speeded decay kinetics. Synaptic NMDAR conditioning was necessary to suppress GABA current in pyramidal neurons; extrasynaptic NMDAR activation did not suppress, even when matched to synaptic activation. We found no evidence that specific synaptic NMDAR subunits mediate depression of GABA responses. Although physical colocalization of glutamate and GABAA receptors is mostly likely in extrasynaptic regions, our evidence suggests that NMDAR-induced suppression of GABA responsiveness prominently affects precise, moment-to-moment signaling from synaptic receptors to synaptic receptors.

scholarly journals Anti-NMDAR encephalitis induced in mice by active immunization with a peptide from amino-terminal domain of the GluN1 subunit

2020 ◽  
Author(s):  
Yuewen Ding ◽  
Zheye Zhou ◽  
Jinyu Chen ◽  
Yu Peng ◽  
Haitao Wang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Hippocampal Neurons ◽  
Calcium Influx ◽  
Memory Loss ◽  
Long Term Potentiation ◽  
Active Immunization ◽  
Amino Terminal ◽  
Terminal Domain ◽  
Nmdar Encephalitis ◽  
Amino Terminal Domain

Abstract Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a recently discovered autoimmune syndrome associated with psychosis, dyskinesia, and seizures. However, the underlying mechanisms of this disease remain unclear, in part because of a lack of suitable animal models. This study describes a novel mouse model of anti-NMDAR encephalitis that was induced by active immunization against NMDARs using amino-terminal domain peptides. After 12 weeks of immunization, the mice showed significant behavioral disorders and memory loss. Furthermore, antibodies from the cerebrospinal fluid of immunized mice lowered the surface NMDAR cluster density in hippocampal neurons. Immunization also impaired long-term potentiation at Schaffer collateral–CA1 synapses and reduced NMDAR-induced calcium influx. This novel mouse model may allow further research into the pathogenesis of anti-NMDAR encephalitis and aid in the development of new therapies for this disease.

scholarly journals The soluble neurexin-1β ectodomain causes calcium influx and augments dendritic outgrowth and synaptic transmission

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Keimpe D. B. Wierda ◽  
Trine L. Toft-Bertelsen ◽  
Casper R. Gøtzsche ◽  
Ellis Pedersen ◽  
Irina Korshunova ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Hippocampal Neurons ◽  
Prolonged Exposure ◽  
Calcium Influx ◽  
Dependent Manner ◽  
Cellular Effects ◽  
Glutamatergic Neurons ◽  
Readily Releasable Pool ◽  
Presynaptic Release ◽  
Activity Dependent

Abstract Classically, neurexins are thought to mediate synaptic connections through trans interactions with a number of different postsynaptic partners. Neurexins are cleaved by metalloproteases in an activity-dependent manner, releasing the soluble extracellular domain. Here, we report that in both immature (before synaptogenesis) and mature (after synaptogenesis) hippocampal neurons, the soluble neurexin-1β ectodomain triggers acute Ca2+-influx at the dendritic/postsynaptic side. In both cases, neuroligin-1 expression was required. In immature neurons, calcium influx required N-type calcium channels and stimulated dendritic outgrowth and neuronal survival. In mature glutamatergic neurons the neurexin-1β ectodomain stimulated calcium influx through NMDA-receptors, which increased presynaptic release probability. In contrast, prolonged exposure to the ectodomain led to inhibition of synaptic transmission. This secondary inhibition was activity- and neuroligin-1 dependent and caused by a reduction in the readily-releasable pool of vesicles. A synthetic peptide modeled after the neurexin-1β:neuroligin-1 interaction site reproduced the cellular effects of the neurexin-1β ectodomain. Collectively, our findings demonstrate that the soluble neurexin ectodomain stimulates growth of neurons and exerts acute and chronic effects on trans-synaptic signaling involved in setting synaptic strength.

Spinophilin limits GluN2B-containing NMDAR activity and sequelae associated with excessive hippocampal NMDAR function

2021 ◽  
Author(s):  
Asma B. Salek ◽  
Ruchi Bansal ◽  
Nicolas F. Berbari ◽  
Anthony J. Baucum
Keyword(s):  
Cognitive Flexibility ◽  
Hippocampal Neurons ◽  
Calcium Influx ◽  
Surface Expression ◽  
List Type ◽  
Dependent Manner ◽  
Caspase Cleavage ◽  
Calcium Dependent ◽  
Apoptotic Pathways

ABSTRACTN-methyl-D-Aspartate receptors (NMDARs) are calcium-permeable ion channels that are ubiquitously expressed within the glutamatergic postsynaptic density. Phosphorylation of NMDAR subunits defines receptor activity and surface localization. Modulation of NMDAR phosphorylation by kinases and phosphatases regulates calcium entering the cell and subsequent activation of calcium-dependent processes. Spinophilin is the major synaptic protein phosphatase 1 (PP1) targeting protein that controls phosphorylation of myriad substrates via targeting or inhibition of PP1. Spinophilin limits NMDAR function in a PP1-dependent manner and we have previously shown that spinophilin sequesters PP1 away from the GluN2B subunit of the NMDAR, which results in increased phosphorylation of Ser-1284. However, how spinophilin modifies NMDAR function is unclear. Herein, we detail that while Ser-1284 phosphorylation increases calcium influx via GluN2B-containing NMDARs, overexpression of spinophilin decreases GluN2B-containing NMDAR activity by decreasing its surface expression. In hippocampal neurons isolated from spinophilin knockout animals there is an increase in cleaved caspase-3 levels compared to wildtype mice; however, this effect is not exclusively due to NMDAR activation; suggesting multiple putative mechanisms by which spinophilin may modulate caspase cleavage. Behaviorally, our data suggest that spinophilin knockout mice have deficits in spatial cognitive flexibility, a behavior associated GluN2B function within the hippocampus. Taken together, our data demonstrate a unique mechanism by which spinophilin modulates GluN2B containing NMDAR phosphorylation, channel function, and trafficking and that loss of spinophilin promotes pathological sequelae associated with GluN2B dysfunction.HIGHLIGHTSSpinophilin bidirectionally regulates GluN2B-containing NMDAR function.Loss of spinophilin in primary hippocampal neurons increases a pro-apoptotic marker.Loss of spinophilin in vivo decreases measures of spatial cognitive flexibility.Graphical AbstractSpinophilin increases the phosphorylation of Ser-1284 on GluN2B, thereby enhancing calcium influx through the GluN2B containing NMDARs. In contrast, spinophilin limits GluN2B-containing surface expression putatively due to modulation of GluN2B interactions with endocytotic proteins. Since the second effect of spinophilin occurs independent of the first, we observe an overall decrease in calcium influx through GluN2B containing NMDARs when spinophilin is present. This low, basal calcium influx is less likely to be promote calcium-dependent activation of caspase and downstream apoptotic pathways and permits flexible search strategies and behaviors. In the absence of spinophilin, the spinophilin-driven internalization of the receptors is decreased, more receptors are expressed on the surface and calcium influx into the cell is increased. This high levels of intracellular calcium triggers apoptotic pathways leading to cell death. This impact may be more dramatic in cells with high expression of GluN2B-containing NMDA receptors. This loss of spinophilin reduces cognitive flexibility in hippocampal dependent tasks.

Bupivacaine and ropivacaine suppress glycine- and glutamate-induced ion currents in acutely dissociated rat hippocampal neurons

2003 ◽  
Vol 344 (1) ◽  
pp. 33-36 ◽  
Author(s):  
Hyeon-Jeong Yang ◽  
Min-Chul Shin ◽  
Hyun-Kyung Chang ◽  
Mi-Hyeon Jang ◽  
Taeck-Hyun Lee ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Ion Currents
Sign in / Sign up

Export Citation Format

Share Document