NMDA Receptor Activation: Two Targets for Two Co-Agonists

Henneberger, Christian; Bard, Lucie; King, Claire; Jennings, Alistair; Rusakov, Dmitri A.

doi:10.1007/s11064-013-0987-2

Cited by 27 publications

(18 citation statements)

References 85 publications

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“…The relative difference in co-agonist use by S-NMDARs and E-NMDARs might be explained by the differential localization of NR2A and NR2B subunits, respectively, as NR2B-containing receptors have a tenfold higher affinity for glycine than NR2A-containing receptors [70,86]. Similarly, the localized release and astrocytic uptake of these coagonists has also been hypothesized to explain the differences in co-agonist use by S-NMDARs vs. ENMDARs (see [87,88] for review). Further work is needed in this area, as a better understanding of the role of NMDAR co-agonists may have therapeutic implications.…”

Section: Synaptic Vs Extrasynaptic Nmdarsmentioning

confidence: 99%

The Role of the Tripartite Glutamatergic Synapse in the Pathophysiology of Alzheimer’s Disease

Rudy¹,

Hunsberger²,

Weitzner³

et al. 2015

Aging and disease

125

104

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Alzheimer's disease (AD) is the most common form of dementia in individuals over 65 years of age and is characterized by accumulation of beta-amyloid (Aβ) and tau. Both Aβ and tau alter synaptic plasticity, leading to synapse loss, neural network dysfunction, and eventually neuron loss. However, the exact mechanism by which these proteins cause neurodegeneration is still not clear. A growing body of evidence suggests perturbations in the glutamatergic tripartite synapse, comprised of a presynaptic terminal, a postsynaptic spine, and an astrocytic process, may underlie the pathogenic mechanisms of AD. Glutamate is the primary excitatory neurotransmitter in the brain and plays an important role in learning and memory, but alterations in glutamatergic signaling can lead to excitotoxicity. This review discusses the ways in which both beta-amyloid (Aβ) and tau act alone and in concert to perturb synaptic functioning of the tripartite synapse, including alterations in glutamate release, astrocytic uptake, and receptor signaling. Particular emphasis is given to the role of N-methyl-D-aspartate (NMDA) as a possible convergence point for Aβ and tau toxicity.

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Section: Synaptic Vs Extrasynaptic Nmdarsmentioning

confidence: 99%

The Role of the Tripartite Glutamatergic Synapse in the Pathophysiology of Alzheimer’s Disease

Rudy¹,

Hunsberger²,

Weitzner³

et al. 2015

Aging and disease

125

104

View full text Add to dashboard Cite

show abstract

“…Astrocytes are multifunctional brain cells that have been implicated in a wide array of important brain functions, including the provision of trophic factors, structural and metabolic support to neurons (Molofsky et al, ; Tsai et al, ; Clarke and Barres, ; Sloan and Barres, ), regulation of vascular tone (Filosa et al, ; Kim et al, ), neurovascular coupling (Attwell et al, ; Petzold and Murthy, ; Otsu et al, ), ion and transmitter clearance (Rose and Karus, ; Sibille et al, , ; Tong et al, ; Murphy‐Royal et al, ), and direct communication with neurons via gliotransmission (Jourdain et al, ; Henneberger et al, ; Shigetomi et al, ; Araque et al, ). Astrocyte interactions with neural elements are important for normal brain development, ongoing function, and plasticity, although many specific mechanistic hypotheses remain controversial (Agulhon et al, ; Petravicz et al, ; Srinivasan et al, ).…”

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confidence: 99%

Spatial organization of astrocytes in ferret visual cortex

López‐Hidalgo

Hoover

Schummers

2016

J of Comparative Neurology

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Astrocytes form an intricate partnership with neural circuits to influence numerous cellular and synaptic processes. One prominent organizational feature of astrocytes is the “tiling” of the brain with non‐overlapping territories. There are some documented species and brain region–specific astrocyte specializations, but the extent of astrocyte diversity and circuit specificity are still unknown. We quantitatively defined the rules that govern the spatial arrangement of astrocyte somata and territory overlap in ferret visual cortex using a combination of in vivo two‐photon imaging, morphological reconstruction, immunostaining, and model simulations. We found that ferret astrocytes share, on average, half of their territory with other astrocytes. However, a specific class of astrocytes, abundant in thalamo‐recipient cortical layers (“kissing” astrocytes), overlap markedly less. Together, these results demonstrate novel features of astrocyte organization indicating that different classes of astrocytes are arranged in a circuit‐specific manner and that tiling does not apply universally across brain regions and species. J. Comp. Neurol. 524:3561–3576, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

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“…In the brain, the endogenous NMDAR coagonist is either d -serine or glycine, with one or the other gating receptors in a nonredundant manner (Henneberger et al 2010, 2013; Kalbaugh et al 2009; Li et al 2009, 2013; Le Bail et al 2015; Meunier et al 2016; Mothet et al 2000; Papouin et al 2012). We investigated coagonist identity within spinal networks by selectively depleting endogenous d -serine.…”

Section: Resultsmentioning

confidence: 99%

Differential regulation of NMDA receptors by d-serine and glycine in mammalian spinal locomotor networks

Acton

Miles

2017

Journal of Neurophysiology

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We provide evidence that NMDARs within murine spinal locomotor networks determine the frequency and amplitude of ongoing locomotor-related activity in vitro and that NMDARs are regulated by d-serine and glycine in a synapse-specific and activity-dependent manner. In addition, glycine transporter-1 is shown to be an important regulator of NMDARs during locomotor-related activity. These results show how excitatory transmission can be tuned to diversify the output repertoire of spinal locomotor networks in mammals.

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NMDA Receptor Activation: Two Targets for Two Co-Agonists

Cited by 27 publications

References 85 publications

The Role of the Tripartite Glutamatergic Synapse in the Pathophysiology of Alzheimer’s Disease

The Role of the Tripartite Glutamatergic Synapse in the Pathophysiology of Alzheimer’s Disease

Spatial organization of astrocytes in ferret visual cortex

Differential regulation of NMDA receptors by d-serine and glycine in mammalian spinal locomotor networks

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