scholarly journals Regulation of Ionotropic Glutamate Receptors by Their Auxiliary Subunits

Physiology ◽  
2010 ◽  
Vol 25 (1) ◽  
pp. 41-49 ◽  
Author(s):  
Susumu Tomita
Keyword(s):  
Synaptic Plasticity ◽  
Synaptic Transmission ◽  
Glutamate Receptors ◽  
Neurological Disorder ◽  
Neural Circuit ◽  
Ionotropic Glutamate Receptors ◽  
Auxiliary Subunits ◽  
The Brain

Glutamate receptors are major excitatory receptors in the brain. Recent findings have established auxiliary subunits of glutamate receptors as critical modulators of synaptic transmission, synaptic plasticity, and neurological disorder. The elucidation of the molecular rules governing glutamate receptors and subunits will improve our understanding of synapses and of neural-circuit regulation in the brain.

scholarly journals Roles of N-Methyl-D-Aspartate Receptors (NMDARs) in Epilepsy

2022 ◽  
Vol 14 ◽  
Author(s):  
Shuang Chen ◽  
Da Xu ◽  
Liu Fan ◽  
Zhi Fang ◽  
Xiufeng Wang ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Glutamate Receptors ◽  
Neurological Disorders ◽  
Nerve Conduction ◽  
Ionotropic Glutamate Receptors ◽  
Future Studies ◽  
Excitatory Neurotransmission ◽  
The Relationship ◽  
Neuron Injury

Epilepsy is one of the most common neurological disorders characterized by recurrent seizures. The mechanism of epilepsy remains unclear and previous studies suggest that N-methyl-D-aspartate receptors (NMDARs) play an important role in abnormal discharges, nerve conduction, neuron injury and inflammation, thereby they may participate in epileptogenesis. NMDARs belong to a family of ionotropic glutamate receptors that play essential roles in excitatory neurotransmission and synaptic plasticity in the mammalian CNS. Despite numerous studies focusing on the role of NMDAR in epilepsy, the relationship appeared to be elusive. In this article, we reviewed the regulation of NMDAR and possible mechanisms of NMDAR in epilepsy and in respect of onset, development, and treatment, trying to provide more evidence for future studies.

scholarly journals Targeting Ionotropic Glutamate Receptors In The Treatment Of Epilepsy

2020 ◽  
Vol 18 ◽  
Author(s):  
Celli Roberta ◽  
Fornai Francesco
Keyword(s):  
Synaptic Transmission ◽  
Glutamate Receptors ◽  
Focal Epilepsy ◽  
Absence Epilepsy ◽  
Excitatory Synaptic Transmission ◽  
Kainate Receptors ◽  
Ionotropic Glutamate Receptors ◽  
Drug Resistant ◽  
Brain Functions ◽  
Nonconvulsive Seizures

Background: A dysfunction in glutamate neurotransmission is critical for seizure. Glutamate is the major excitatory drive in the cerebral cortex, where seizures occur. Glutamate acts via (i) ionotropic (iGlu) receptors, which are ligand-gated ion channels mediating fast excitatory synaptic transmission; and (ii) G proteins coupled metabotropic (mGlu) receptors. Objective: To overview the evidence on the role of iGlu receptors in the onset, duration, and severity of convulsive and nonconvulsive seizures to lay the groundwork for novel strategies for drug-resistant epilepsy. Methods: We used PubMed crossed-search for “glutamate receptor and epilepsy” (sorting 3,170 reports), searched for “ionotropic glutamate receptors”, “AMPA receptors”, “NMDA receptors”, “kainate receptors”, “convulsive seizures”, “absence epilepsy”, and selected those papers focusing this Review’s scope. Results: iGlu receptors antagonists inhibit, whereas agonists worsen experimental seizures in various animal species. Clinical development of iGlu receptor antagonists has been limited by the occurrence of adverse effects caused by inhibition of fast excitatory synaptic transmission. To date, only one drug (perampanel) selectively targeting iGlu receptors is marketed for the treatment of focal epilepsy. However, other drugs, such as topiramate and felbamate, inhibit iGlu receptors in addition to other mechanisms. Conclusion: This review is expected to help dissecting those steps induced by iGlu receptors activation, which may be altered to provide antiepileptic efficacy without altering key physiological brain functions, thus improving safety and tolerability of iGlu-receptor directed antiepileptic agents. This effort mostly applies to drug resistant seizures, which impact the quality of life and often lead to status epilepticus, which is a medical urgency.

scholarly journals Learning efficient task-dependent representations with synaptic plasticity

2020 ◽  
Author(s):  
Colin Bredenberg ◽  
Eero P. Simoncelli ◽  
Cristina Savin
Keyword(s):  
Synaptic Plasticity ◽  
High Performance ◽  
Neural Circuit ◽  
Intrinsic Noise ◽  
Relevant Information ◽  
Task Structure ◽  
Neural Populations ◽  
The Brain ◽  
Different Levels ◽  
And Task

AbstractNeural populations do not perfectly encode the sensory world: their capacity is limited by the number of neurons, metabolic and other biophysical resources, and intrinsic noise. The brain is presumably shaped by these limitations, improving efficiency by discarding some aspects of incoming sensory streams, while prefer-entially preserving commonly occurring, behaviorally-relevant information. Here we construct a stochastic recurrent neural circuit model that can learn efficient, task-specific sensory codes using a novel form of reward-modulated Hebbian synaptic plasticity. We illustrate the flexibility of the model by training an initially unstructured neural network to solve two different tasks: stimulus estimation, and stimulus discrimination. The network achieves high performance in both tasks by appropriately allocating resources and using its recurrent circuitry to best compensate for different levels of noise. We also show how the interaction between stimulus priors and task structure dictates the emergent network representations.

Long-Term Potentiation and Long-Term Depression

2018 ◽  
Author(s):  
Arianna Maffei
Keyword(s):  
Synaptic Plasticity ◽  
Neural Circuit ◽  
Long Term Potentiation ◽  
Synaptic Connections ◽  
Long Term Depression ◽  
Term Potentiation ◽  
Functional Implications ◽  
The Brain

Synaptic connections in the brain can change their strength in response to patterned activity. This ability of synapses is defined as synaptic plasticity. Long lasting forms of synaptic plasticity, long-term potentiation (LTP), and long-term depression (LTD), are thought to mediate the storage of information about stimuli or features of stimuli in a neural circuit. Since its discovery in the early 1970s, synaptic plasticity became a central subject of neuroscience, and many studies centered on understanding its mechanisms, as well as its functional implications.

scholarly journals Species-specific differences in synaptic transmission and plasticity

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Prateep Beed ◽  
Saikat Ray ◽  
Laura Moreno Velasquez ◽  
Alexander Stumpf ◽  
Daniel Parthier ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Synaptic Transmission ◽  
Mossy Fiber ◽  
Mossy Fibers ◽  
Evolutionary Divergence ◽  
Short Term Plasticity ◽  
Species Specific ◽  
The Brain ◽  
Lower Expression

Abstract Synaptic transmission and plasticity in the hippocampus are integral factors in learning and memory. While there has been intense investigation of these critical mechanisms in the brain of rodents, we lack a broader understanding of the generality of these processes across species. We investigated one of the smallest animals with conserved hippocampal macroanatomy—the Etruscan shrew, and found that while synaptic properties and plasticity in CA1 Schaffer collateral synapses were similar to mice, CA3 mossy fiber synapses showed striking differences in synaptic plasticity between shrews and mice. Shrew mossy fibers have lower long term plasticity compared to mice. Short term plasticity and the expression of a key protein involved in it, synaptotagmin 7 were also markedly lower at the mossy fibers in shrews than in mice. We also observed similar lower expression of synaptotagmin 7 in the mossy fibers of bats that are evolutionarily closer to shrews than mice. Species specific differences in synaptic plasticity and the key molecules regulating it, highlight the evolutionary divergence of neuronal circuit functions.

scholarly journals Neurosteroid modulation of ionotropic glutamate receptors and excitatory synaptic transmission

2008 ◽  
pp. S49-S57
Author(s):  
M Sedláček ◽  
M Kořínek ◽  
M Petrovič ◽  
O Cais ◽  
E Adamusová ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Nmda Receptors ◽  
Glutamate Receptors ◽  
Ampa Receptors ◽  
Transmembrane Domain ◽  
Kainate Receptors ◽  
Ionotropic Glutamate Receptors ◽  
Extracellular Loop ◽  
Inhibitory Effects ◽  
Chimeric Receptors

Ionotropic glutamate receptors function can be affected by neurosteroids, both positively and negatively. N-methyl-D-aspartate (NMDA) receptor responses to exogenously applied glutamate are potentiated or inhibited (depending on the receptor subunit composition) by pregnenolone sulphate (PS) and inhibited by pregnanolone sulphate (3alpha5betaS). While PS effect is most pronounced when its application precedes that of glutamate, 3alpha5betaS only binds to receptors already activated. Synaptically activated NMDA receptors are inhibited by 3alpha5betaS, though to a lesser extent than those tonically activated by exogenous glutamate. PS, on the other hand, shows virtually no effect on any of the models of synaptically activated NMDA receptors. The site of neurosteroid action at the receptor molecule has not yet been identified, however, the experiments indicate that there are at least two distinct extracellularly located binding sites for PS mediating its potentiating and inhibitory effects respectively. Experiments with chimeric receptors revealed the importance of the extracellular loop connecting the third and the fourth transmembrane domain of the receptor NR2 subunit for the neurosteroid action. alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptors are inhibited by both PS and 3alpha5betaS. These neurosteroids also affect AMPA receptors-mediated synaptic transmission, however, in a rather indirect way, through presynaptically located targets of action.

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