scholarly journals Visualization of NMDA receptor–dependent AMPA receptor synaptic plasticity in vivo

2015 ◽  
Vol 18 (3) ◽  
pp. 402-407 ◽  
Author(s):  
Yong Zhang ◽  
Robert H Cudmore ◽  
Da-Ting Lin ◽  
David J Linden ◽  
Richard L Huganir
Keyword(s):  
Synaptic Plasticity ◽  
Nmda Receptor ◽  
Ampa Receptor

Dopaminergic D2 receptors activate PKA to inhibit spinal pelvic-urethra reflex in rats

2010 ◽  
Vol 299 (3) ◽  
pp. F681-F686 ◽  
Author(s):  
Hsi-Chin Wu ◽  
Chun-Hsien Chiu ◽  
Kwong-Chung Tung ◽  
Gin-Den Chen ◽  
Hsien-Yu Peng ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Ampa Receptor ◽  
Receptor Agonist ◽  
Repetitive Stimulation ◽  
Spinal Reflex ◽  
External Urethral Sphincter ◽  
Urethral Closure ◽  
Dependent Inhibition

To clarify the role of descending dopaminergic innervation in reflexive urethral closure, the impacts of dopaminergic D2 receptor (DR2)-selective agonists and antagonists on repetitive stimulation-induced pelvic-to-urethra spinal reflex potentiation (SRP) were tested using in vivo rat preparations. Pelvic afferent nerve test stimulation (TS; 1 pulse/30 s for 30 min) evoked baseline reflex activity with single spikes in the external urethral sphincter electromyogram (EUSE), whereas, repetitive stimulation (RS; 1 pulse/s for 30 min) induced SRP. Intrathecal application of quinelorane dihydrochloride (Q110; 10, 30, and 100 nM, 10 μl, a selective DR2 agonist) dose dependently inhibited the RS-induced SRP. Pretreatment with L135 (100 nM, 10 μL it, a selective DR2 antagonist) antagonized the Q110-dependent inhibition (100 nM, 10 μl it). Intrathecal AMPA (10 μM, 10 μl, a selective glutamatergic AMPA receptor agonist), and NMDA (10 μM, 10 μl, a selective glutamatergic NMDA receptor agonist) reversed the Q110-dependent inhibition. Intrathecal forskolin (100 nM, 10 μl, a PKA activator) prevented the Q110-dependent inhibition that was reversed by CNQX (10 μM, 10 μl it, a selective glutamate AMPA receptor antagonist) and APV (10 μM, 10 μl it , a selective glutamate NMDA receptor antagonist). Our results suggest that DR2 activation, which inactivates intracellular PKA, may be involved in descending dopaminergic inhibition of NMDA/AMPA receptor-dependent SRP at the lumbosacral spinal cord, which is thought to be involved in reflexive urethral closure.

scholarly journals DL-3-n-butylphthalide enhances synaptic plasticity in mouse model of brain impairments

STEMedicine ◽  
2022 ◽  
Vol 3 (1) ◽  
pp. e113
Author(s):  
Qian Ding ◽  
Qian Yu ◽  
Lei Tao ◽  
Yifei Guo ◽  
Juan Zhao ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Nmda Receptor ◽  
Glutamate Release ◽  
Field Potential ◽  
Nmda Receptor Subunits ◽  
Glutamate Level ◽  
Regulatory Effects ◽  
Glutaminase Activity

Synaptic impairment results in cognitive dysfunction of Alzheimer’s disease (AD). As a plant extract, it is found that DL-3-n-butylphthalide (L-NBP) rescues abnormal cognitive behaviors in AD animals. However, the regulatory effects of L-NBP on synaptic plasticity remains unclear. APP/PS1 mice at 12 months old received oral L-NBP treatment for 12 weeks. A water maze test assessed cognitive performances. In vitro patch-clamp recordings and in vivo field potential recordings were performed to evaluate synaptic plasticity. The protein expression of AMPA receptor subunits (GluR1 and GluR2) and NMDA receptor subunits (NR1, NR2A, and NR2B) was examined by Western blot. In addition, glutaminase activity and glutamate level in the hippocampus were measured by colorimetry to evaluate presynaptic glutamate release. L-NBP treatment could significantly improve learning and memory ability, upregulate NR2A and NR2B protein expressions, increase glutaminase activity and glutamate level in the hippocampus, and attenuate synaptic impairment transmission in the AD mice. L-NPB plays a beneficial role in AD mice by regulating NMDA receptor subunits’ expression and regulating presynaptic glutamate release.

scholarly journals Distinct Modes of AMPA Receptor Suppression at Developing Synapses by GluN2A and GluN2B: Single-Cell NMDA Receptor Subunit Deletion In Vivo

Neuron ◽  
2011 ◽  
Vol 71 (6) ◽  
pp. 1085-1101 ◽  
Author(s):  
John A. Gray ◽  
Yun Shi ◽  
Hiroshi Usui ◽  
Matthew J. During ◽  
Kenji Sakimura ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Single Cell ◽  
Ampa Receptor ◽  
Receptor Subunit ◽  
Nmda Receptor Subunit

scholarly journals Tyrosine phosphorylation of the AMPA receptor subunit GluA2 gates homeostatic synaptic plasticity

2020 ◽  
Vol 117 (9) ◽  
pp. 4948-4958 ◽  
Author(s):  
Adeline J. H. Yong ◽  
Han L. Tan ◽  
Qianwen Zhu ◽  
Alexei M. Bygrave ◽  
Richard C. Johnson ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Ampa Receptor ◽  
Phosphorylation Site ◽  
Long Term Potentiation ◽  
Interacting Protein ◽  
Hebbian Plasticity ◽  
Term Potentiation ◽  
Ampa Receptor Subunit

Hebbian plasticity, comprised of long-term potentiation (LTP) and depression (LTD), allows neurons to encode and respond to specific stimuli; while homeostatic synaptic scaling is a counterbalancing mechanism that enables the maintenance of stable neural circuits. Both types of synaptic plasticity involve the control of postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAR) abundance, which is modulated by AMPAR phosphorylation. To address the necessity of GluA2 phospho-Y876 in synaptic plasticity, we generated phospho-deficient GluA2 Y876F knock-in mice. We show that, while GluA2 phospho-Y876 is not necessary for Hebbian plasticity, it is essential for both in vivo and in vitro homeostatic upscaling. Bidirectional changes in GluA2 phospho-Y876 were observed during homeostatic scaling, with a decrease during downscaling and an increase during upscaling. GluA2 phospho-Y876 is necessary for synaptic accumulation of glutamate receptor interacting protein 1 (GRIP1), a crucial scaffold protein that delivers AMPARs to synapses, during upscaling. Furthermore, increased phosphorylation at GluA2 Y876 increases GluA2 binding to GRIP1. These results demonstrate that AMPAR trafficking during homeostatic upscaling can be gated by a single phosphorylation site on the GluA2 subunit.

scholarly journals Stretch injury selectively enhances extrasynaptic, GluN2B-containing NMDA receptor function in cortical neurons

2013 ◽  
Vol 110 (1) ◽  
pp. 131-140 ◽  
Author(s):  
Carrie R. Ferrario ◽  
Blaise O. Ndukwe ◽  
Jianhua Ren ◽  
Leslie S. Satin ◽  
Paulette B. Goforth
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Ampa Receptor ◽  
Cortical Neurons ◽  
Mechanical Stretch ◽  
Receptor Activity ◽  
Network Activity ◽  
Stretch Injury

Alterations in the function and expression of NMDA receptors are observed after in vivo and in vitro traumatic brain injury. We recently reported that mechanical stretch injury in cortical neurons transiently increases the contribution of NMDA receptors to network activity and results in an increase in calcium-permeable AMPA (CP-AMPA) receptor-mediated transmission 4 h postinjury ( Goforth et al. 2011 ). Here, we evaluated changes in the function of synaptic vs. extrasynaptic GluN2B-containing NMDA receptors after injury. We also determined whether postinjury treatment with the GluN2B-selective antagonist Ro 25-6981 or memantine prevents injury-induced increases in CP-AMPA receptor activity. We found that injury increased extrasynaptic, GluN2B-containing NMDA receptor-mediated whole cell currents. In contrast, we found no differences in synaptic NMDA receptor-mediated transmission after injury. Furthermore, treatment with Ro 25-6981 or memantine after injury prevented injury-induced increases in CP-AMPA receptor-mediated activity. Together, our data suggest that increased NMDA receptor activity after injury is predominantly due to alterations in extrasynaptic, GluN2B-containing NMDA receptors and that activation of these receptors may contribute to the appearance of CP-AMPA receptors after injury.

scholarly journals Lrfn2-mutant mice display suppressed synaptic plasticity and inhibitory synapse development and abnormal social communication and startle response

2018 ◽  
Author(s):  
Yan Li ◽  
Ryunhee Kim ◽  
Yi Sul Cho ◽  
Doyoun Kim ◽  
Kyungdeok Kim ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Nmda Receptor ◽  
Synaptic Transmission ◽  
Social Communication ◽  
Acoustic Startle ◽  
Ultrasonic Vocalization ◽  
Inhibitory Synapse ◽  
Excitatory Synapse ◽  
Synapse Development

AbstractSALM1, also known as LRFN2, is a PSD-95-interacting synaptic adhesion molecule implicated in the regulation of NMDA receptor (NMDAR) clustering largely based on in vitro data, although its in vivo functions remain unclear. Here, we found that mice lacking SALM1/LRFN2 (Lrfn2-/- mice) show a normal density of excitatory synapses but altered excitatory synaptic function, including enhanced NMDAR-dependent synaptic transmission but suppressed NMDAR-dependent synaptic plasticity in the hippocampal CA1 region. Unexpectedly, SALM1 expression is detected in both glutamatergic and GABAergic neurons, and Lrfn2-/- CA1 pyramidal neurons show decreases in the density of inhibitory synapses and frequency of spontaneous inhibitory synaptic transmission. Behaviorally, ultrasonic vocalization was suppressed in Lrfn2-/- pups separated from their mothers, and acoustic startle was enhanced, but locomotion, anxiety-like behavior, social interaction, repetitive behaviors, and learning and memory were largely normal in adult Lrfn2-/- mice. These results suggest that SALM1/LRFN2 regulates excitatory synapse function, inhibitory synapse development, and social communication and startle behaviors in mice.Significance StatementSynaptic adhesion molecules regulate synapse development and function, which govern neural circuit and brain functions. The SALM/LRFN family of synaptic adhesion proteins consists of five known members whose in vivo functions are largely unknown. Here we characterized mice lacking SALM1/LRFN2 (SALM1 knockout) known to associate with NMDA receptors and found that these mice showed altered NMDA receptor-dependent synaptic transmission and plasticity, as expected, but unexpectedly also exhibited suppressed inhibitory synapse development and synaptic transmission. Behaviorally, SALM1 knockout pups showed suppressed ultrasonic vocalization upon separation from their mothers, and SALM1 knockout adults showed enhanced responses to loud acoustic stimuli. These results suggest that SALM1/LRFN2 regulates excitatory synapse function, inhibitory synapse development, social communication, and acoustic startle behavior.

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