Faculty Opinions recommendation of Evolutionary conserved role for TARPs in the gating of glutamate receptors and tuning of synaptic function.

1. In the retina, as in other regions of the vertebrate central nervous system, glutamate receptors mediate excitatory chemical synaptic transmission and are a critical site for the regulation of cellular communication. In this study, retinal horizontal cells from the hybrid less were dissociated in cell culture, voltage clamped by the whole cell recording technique, and the currents evoked by application of excitatory amino acids recorded. 2. Responses to glutamate and its agonist kainate were reduced by approximately 50% in the presence of the nitric oxide (NO) donors sodium nitroprusside and S-nitroso-N-acetylpenicillamine. The effect of these compounds was blocked by the NO scavenger hemoglobin. 3. This effect of NO donors on kainate currents could be mimicked by the application of a membrane permeable guanosine 3',5'-cyclic monophosphate (cGMP) analogue, 8-Br-cGMP. The NO effect was also blocked by application of the guanylate cyclase inhibitor LY-83583, and by a protein kinase G inhibitor peptide. 4. In H1-type horizontal cells, stimulation of endogenous nitric oxide synthase with L-arginine reduced kainate responses, whereas application of D-arginine had no effect. 5. This receptor modulation mechanism may act in concert with other pre- and postsynaptic mechanisms to modify horizontal cell synaptic function according to the adaptational state of the retina and also may protect horizontal cells from glutamate excitotoxicity.

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Overexpression of Human SNX27 Enhances Learning and Memory Through Modulating Synaptic Plasticity in Mice

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.595357 ◽

2020 ◽

Vol 8 ◽

Author(s):

Yuanhui Huo ◽

Yue Gao ◽

Qiuyang Zheng ◽

Dongdong Zhao ◽

Tiantian Guo ◽

...

Keyword(s):

Synaptic Transmission ◽

Glutamate Receptors ◽

Learning And Memory ◽

Neurological Diseases ◽

Adaptor Protein ◽

Long Term Potentiation ◽

Postsynaptic Membrane ◽

Synaptic Function ◽

Membrane Receptors ◽

Sorting Nexin

Abnormal synaptic transmission leads to learning and memory disorders and is the main feature of neurological diseases. Sorting nexin 27 (SNX27) is an endosomal adaptor protein associated with a variety of nervous system diseases, and it is mainly responsible for the trafficking of postsynaptic membrane receptors. However, the roles of SNX27 in regulating synaptic and cognitive function are not fully understood. Here, we first generated a neuron-specific human-SNX27 transgenic mouse model (hSNX27 Tg) that exhibited enhanced excitatory synaptic transmission and long-term potentiation (LTP). In addition, we found that the hSNX27 Tg mice displayed enhanced learning and memory, lower-level anxiety-like behavior, and increased social interaction. Furthermore, we found that SNX27 overexpression upregulated the expression of glutamate receptors in the cortex and hippocampus of hSNX27 Tg mice. Together, these results indicate that SNX27 overexpression promotes synaptic function and cognition through modulating glutamate receptors.

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Evolutionary Conserved Role for TARPs in the Gating of Glutamate Receptors and Tuning of Synaptic Function

Neuron ◽

10.1016/j.neuron.2008.07.023 ◽

2008 ◽

Vol 59 (6) ◽

pp. 997-1008 ◽

Cited By ~ 38

Author(s):

Rui Wang ◽

Craig S. Walker ◽

Penelope J. Brockie ◽

Michael M. Francis ◽

Jerry E. Mellem ◽

...

Keyword(s):

Glutamate Receptors ◽

Synaptic Function

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Postsynaptic neuronal geometry and synaptic effectiveness

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100127840 ◽

1987 ◽

Vol 45 ◽

pp. 690-697

Author(s):

C.J. Wilson

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Synaptic Function ◽

Postsynaptic Neuron ◽

Synaptic Inputs ◽

Partial Analysis ◽

Postsynaptic Cell ◽

Neuronal Geometry ◽

The Relationship ◽

Complex Scale

Most central nervous system neurons receive synaptic input from hundreds or thousands of other neurons, and the computational function of such neurons results from the interactions of inputs on a large and complex scale. In most situations that have yielded to a partial analysis, the synaptic inputs to a neuron are not alike in function, but rather belong to distinct categories that differ qualitatively in the nature of their effect on the postsynaptic cell, and quantitatively in the strength of their influence. Many factors have been demonstrated to contribute to synaptic function, but one of the simplest and best known of these is the geometry of the postsynaptic neuron. The fundamental nature of the relationship between neuronal shape and synaptic effectiveness was established on theoretical grounds prior to its experimental verification.

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Three-dimensional structure of dendritic spines, neuronal specializations that impart both stability and flexibility to synaptic function

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100146308 ◽

1993 ◽

Vol 51 ◽

pp. 92-93

Author(s):

Kristen M. Harris

Keyword(s):

Dendritic Spines ◽

Three Dimensional ◽

Synaptic Function ◽

Dimensional Structure ◽

Excitatory Synapses ◽

Concept Of Function ◽

Section Electron ◽

High Quality Information ◽

The Central Nervous System ◽

Mathematical Analyses

Dendritic spines are the tiny protrusions that stud the surface of many neurons and they are the location of over 90% of all excitatory synapses that occur in the central nervous system. Their small size and variable shapes has in large part made detailed study of their structure refractory to conventional light microscopy and single section electron microscopy (EM). Yet their widespread occurrence and likely involvement in learning and memory has motivated extensive efforts to obtain quantitative descriptions of spines in both steady state and dynamic conditions. Since the seminal mathematical analyses of D’Arcy Thompson, the power of establishing quantitatively key parameters of structure has become recognized as a foundation of successful biological inquiry. For dendritic spines highly precise determinations of structure and its variation are proving themselves as the kingpin for establishing a valid concept of function. The recent conjunction of high quality information about the structure, function, and theoretical implications of dendritic spines has produced a flurry of new considerations of their role in synaptic transmission.

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426: Potential Signal Generation Through Metabotropic Glutamate Receptors by Prostate Specific Membrane Antigen

The Journal of Urology ◽

10.1016/s0022-5347(18)37688-2 ◽

2004 ◽

Vol 171 (4S) ◽

pp. 112-112

Author(s):

Aaron Milbank ◽

Mike Aleman ◽

Kelley Harsch ◽

Nick Detore ◽

Eric A. Klein ◽

...

Keyword(s):

Glutamate Receptors ◽

Metabotropic Glutamate Receptors ◽

Signal Generation ◽

Prostate Specific Membrane Antigen ◽

Metabotropic Glutamate ◽

Potential Signal ◽

Specific Membrane

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Two-photon functional mapping of glutamate receptors in cerebellar Purkinje cells in slice

Neuroscience Research ◽

10.1016/s0168-0102(00)81024-x ◽

2000 ◽

Vol 38 ◽

pp. S29

Author(s):

M Matsuzaki

Keyword(s):

Glutamate Receptors ◽

Purkinje Cells ◽

Functional Mapping ◽

Two Photon ◽

Cerebellar Purkinje Cells

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Glioblastoma invasion and NMDA receptors: A novel prospect

Physiology International ◽

10.1556/2060.106.2019.22 ◽

2019 ◽

Vol 106 (3) ◽

pp. 250-260 ◽

Cited By ~ 3

Author(s):

DN Nandakumar ◽

P Ramaswamy ◽

C Prasad ◽

D Srinivas ◽

K Goswami

Keyword(s):

Glutamate Receptors ◽

Cell Lines ◽

Intracellular Signaling ◽

Transcript Level ◽

Glioblastoma Cells ◽

Invasion And Migration ◽

Matrigel Invasion ◽

Nmdar Activation ◽

And Migration

Purpose Glioblastoma cells create glutamate-rich tumor microenvironment, which initiates activation of ion channels and modulates downstream intracellular signaling. N-methyl-D-aspartate receptors (NMDARs; a type of glutamate receptors) have a high affinity for glutamate. The role of NMDAR activation on invasion of glioblastoma cells and the crosstalk with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is yet to be explored. Main methods LN18, U251MG, and patient-derived glioblastoma cells were stimulated with NMDA to activate NMDAR glutamate receptors. The role of NMDAR activation on invasion and migration and its crosstalk with AMPAR were evaluated. Invasion and migration of glioblastoma cells were investigated by in vitro trans-well Matrigel invasion and trans-well migration assays, respectively. Expression of NMDARs and AMPARs at transcript level was evaluated by quantitative real-time polymerase chain reaction. Results We determined that NMDA stimulation leads to enhanced invasion in LN18, U251MG, and patient-derived glioblastoma cells, whereas inhibition of NMDAR using MK-801, a non-competitive antagonist of the NMDAR, significantly decreased the invasive capacity. Concordant with these findings, migration was significantly augmented by NMDAR in both cell lines. Furthermore, NMDA stimulation upregulated the expression of GluN2 and GluA1 subunits at the transcript level. Conclusions This study demonstrated the previously unexplored role of NMDAR in invasion of glioblastoma cells. Furthermore, the expression of the GluN2 subunit of NMDAR and the differential overexpression of the GluA1 subunit of AMPAR in both cell lines provide a plausible rationale of crosstalk between these calcium-permeable subunits in the glutamate-rich microenvironment of glioblastoma.

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