Activity‐dependent synaptic plasticity of NMDA receptors

Rebola, Nelson; Srikumar, B.N.; Mulle, Christophe

doi:10.1113/jphysiol.2009.179382

Cited by 141 publications

(103 citation statements)

References 62 publications

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“…Functional NMDARs have a crucial role in the induction of long-term potentiation (LTP), namely synaptic plasticity, which underlie memory and learning (Rebola et al, 2010). On the other hand, overactivation of NMDARs leads to cytosolic free intracellular calcium overload, causing excitotoxicity in the central nervous system (Parameshwaran et al, 2008).…”

Section: Hps Treatment Reverses the Changes In Level Of Nmda Subunitsmentioning

confidence: 99%

Cognitive-enhancing effects of hydrolysate of polygalasaponin in SAMP8 mice

Wang

et al. 2016

J. Zhejiang Univ. Sci. B

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Abstract:Objectives: The aim of the study is to evaluate the cognitive-enhancing effects of hydrolysate of polygalasaponin (HPS) on senescence accelerate mouse P8 (SAMP8) mice, an effective Alzheimer's disease (AD) model, and to research the relevant mechanisms. Methods: The cognitive-enhancing effects of HPS on SAMP8 mice were assessed using Morris water maze (MWM) and step-through passive avoidance tests. Then N-methyl-D-aspartate (NMDA) receptor subunit expression for both the cortex and hippocampus of mice was observed using Western blotting. Results: HPS (25 and 50 mg/kg) improved the escape rate and decreased the escape latency and time spent in the target quadrant for the SAMP8 mice in the MWM after oral administration of HPS for 10 d. Moreover, it decreased error times in the passive avoidance tests. Western blotting showed that HPS was able to reverse the levels of NMDAR1 and NMDAR2B expression in the cortex or hippocampus of model mice. Conclusions: The present study suggested that HPS can improve cognitive deficits in SAMP8 mice, and this mechanism might be associated with NMDA receptor (NMDAR)-related pathways.

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Section: Hps Treatment Reverses the Changes In Level Of Nmda Subunitsmentioning

confidence: 99%

Cognitive-enhancing effects of hydrolysate of polygalasaponin in SAMP8 mice

Wang

et al. 2016

J. Zhejiang Univ. Sci. B

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“…This is achieved mainly via glutamate's action on two types of receptors: N-methyl-D-aspartate (NMDAR) and α-amino-3-hydroxy-5-methylisoazol-4-propionate (AMPAR) (10,11). The balance between the activity of these receptors was proposed to determine neuronal firing synchrony (12, 13), with high NMDAR activity associated with desynchrony reminiscent of active wakefulness and low NMDAR linked to synchrony, similar to intense NREM sleep (14).…”

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confidence: 99%

Neuroligin-1 links neuronal activity to sleep-wake regulation

Helou

Bélanger-Nelson

Freyburger

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

104

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Maintaining wakefulness is associated with a progressive increase in the need for sleep. This phenomenon has been linked to changes in synaptic function. The synaptic adhesion molecule Neuroligin-1 (NLG1) controls the activity and synaptic localization of N-methyl-Daspartate receptors, which activity is impaired by prolonged wakefulness. We here highlight that this pathway may underlie both the adverse effects of sleep loss on cognition and the subsequent changes in cortical synchrony. We found that the expression of specific Nlg1 transcript variants is changed by sleep deprivation in three mouse strains. These observations were associated with strainspecific changes in synaptic NLG1 protein content. Importantly, we showed that Nlg1 knockout mice are not able to sustain wakefulness and spend more time in nonrapid eye movement sleep than wild-type mice. These changes occurred with modifications in waking quality as exemplified by low theta/alpha activity during wakefulness and poor preference for social novelty, as well as altered delta synchrony during sleep. Finally, we identified a transcriptional pathway that could underlie the sleep/wake-dependent changes in Nlg1 expression and that involves clock transcription factors. We thus suggest that NLG1 is an element that contributes to the coupling of neuronal activity to sleep/wake regulation.ChIP | EEG | gene expression | sleep homeostasis | synaptic plasticity S leep is crucial for learning, memory, and other functions essential for proper functioning of the brain and body (1, 2). These functions have been associated with the sleep recovery process, which defines a level of pressure for sleep that increases with wakefulness and dissipates during sleep and that is reflected by changes in sleep intensity (3, 4). Sleep intensity is indexed by electroencephalographic (EEG) markers of neuronal synchrony in delta frequencies (1-4 Hz) measured during nonrapid eye movement (NREM) sleep (5). During wakefulness, mechanisms favoring desynchrony in the delta range predominate, and the brain can maintain cognition, whereas during sleep, events promoting network synchrony mostly take place with high delta activity thought to be permissive of recovery (3, 6). The sleep recovery process has been hypothesized to originate and contribute to the maintenance of both synaptic and network equilibrium (6-8). This notion is supported by the observation that specific plasticityrelated genes may be directly involved in regulating sleep need (9). Certain clock genes may also directly contribute, in a circadian-independent manner, to the sleep recovery process (5, 9). However, the mechanisms underlying the capacity and requirement of the brain to switch from an alert desynchronized state to an unconscious synchronized state remain elusive.Glutamate, the main excitatory neurotransmitter of the brain, can induce long-term modifications of synaptic transmission and, thus, changes in network connectivity. This is achieved mainly via glutamate's action on two types of receptors: N-methyl-D-aspa...

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“…The NMDAR subtype of glutamate (GLU) receptors is widely expressed in the central nervous system (CNS) and has a cardinal role in activity-dependent changes in synaptic strength and connectivity underlying higher brain functions such as memory and learning [6,7]. Unlike other neurotransmitter receptors, which are activated by individual neurotransmitters, NMDARs activation requires, in addition to the agonist GLU, the binding of a coagonist which was originally thought to be GLY [8,9].…”

Section: Introductionmentioning

confidence: 99%

D-Serine in Neuropsychiatric Disorders: New Advances

Durrant

Heresco-Levy

2014

Advances in Psychiatry

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D-Serine (DSR) is an endogenous amino acid involved in glia-synapse interactions that has unique neurotransmitter characteristics. DSR acts as obligatory coagonist at the glycine site associated with the N-methyl-D-aspartate subtype of glutamate receptors (NMDAR) and has a cardinal modulatory role in major NMDAR-dependent processes including NMDAR-mediated neurotransmission, neurotoxicity, synaptic plasticity, and cell migration. Since either over-or underfunction of NMDARs may be involved in the pathophysiology of neuropsychiatric disorders; the pharmacological manipulation of DSR signaling represents a major drug development target. A first generation of proof-of-concept animal and clinical studies suggest beneficial DSR effects in treatmentrefractory schizophrenia, movement, depression, and anxiety disorders and for the improvement of cognitive performance. A related developing pharmacological strategy is the indirect modification of DSR synaptic levels by use of compounds that alter the function of main enzymes responsible for DSR production and degradation. Accumulating data indicate that, during the next decade, we will witness important advances in the understanding of DSR role that will further contribute to elucidating the causes of neuropsychiatric disorders and will be instrumental in the development of innovative treatments.

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Activity‐dependent synaptic plasticity of NMDA receptors

Cited by 141 publications

References 62 publications

Cognitive-enhancing effects of hydrolysate of polygalasaponin in SAMP8 mice

Cognitive-enhancing effects of hydrolysate of polygalasaponin in SAMP8 mice

Neuroligin-1 links neuronal activity to sleep-wake regulation

D-Serine in Neuropsychiatric Disorders: New Advances

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