Active release of glycine or <scp>d</scp>‐serine saturates the glycine site of NMDA receptors at the cerebellar mossy fibre to granule cell synapse

Billups, Daniela; Attwell, David

doi:10.1111/j.1460-9568.2003.02996.x

Cited by 36 publications

(38 citation statements)

References 46 publications

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“…Furthermore, exogenous D-serine rescued LTP and LTD in Grin1 mutants expressing a lower NMDA-NR1 D-serine affinity, indicating that exogenous D-serine application substantially increased the intra-synaptic D-serine concentration. That this treatment had no effect on submaximal LTP in wild-type mice indicates that D-serine is normally not the limiting factor for NMDA receptor activation during tetanic stimulation (Billups and Attwell, 2003).…”

Section: Specific Regulation Of Nmda-nr2b-dependent Ltd By Extracellumentioning

confidence: 99%

D-Serine Augments NMDA-NR2B Receptor-Dependent Hippocampal Long-Term Depression and Spatial Reversal Learning

Duffy

Labrie

Roder

2007

Neuropsychopharmacol

157

135

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The contributions of hippocampal long-term depression (LTD) to explicit learning and memory are poorly understood. Electrophysiological and behavioral studies examined the effects of modulating NMDA receptor-dependent LTD on spatial learning in the Morris water maze (MWM). The NMDA receptor co-agonist D-serine substantially enhanced NR2B-dependent LTD, but not long-term potentiation (LTP) or depotentiation, in hippocampal slices from adult wild type mice. Exogenous D-serine did not alter MWM acquisition, but substantially enhanced subsequent reversal learning of a novel target location and performance in a delayed-matchingto-place task. Conversely, an NR2B antagonist disrupted reversal learning and promoted perseveration. Endogenous synaptic D-serine likely saturates during LTP induction because exogenous D-serine rescued deficient LTP and MWM acquisition in Grin1 D481N mutant mice having a lower D-serine affinity. Thus, D-serine may enhance a form of hippocampal NR2B-dependent LTD that contributes to spatial reversal learning. By enhancing this form of synaptic plasticity, D-serine could improve cognitive flexibility in psychiatric disorders characterized by perseveration of aberrant ideation or behaviors.

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Section: Specific Regulation Of Nmda-nr2b-dependent Ltd By Extracellumentioning

confidence: 99%

D-Serine Augments NMDA-NR2B Receptor-Dependent Hippocampal Long-Term Depression and Spatial Reversal Learning

Duffy

Labrie

Roder

2007

Neuropsychopharmacol

157

135

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“…These receptor assemblies mediate transmembrane flux of Na 1 , Ca 21 , and K 1 in a manner that is allosterically regulated by Mg 21 , Zn 21 , H 1 , polyamines, and a socalled glycine coagonist binding site that can be activated by either glycine or D-serine. Although glycine may be the dominant coagonist in cerebellum (Schell et al, 1997), strong consensus indicates that D-serine is the major endogenous NMDA receptor coagonist in other brain regions examined (Brugger et al, 1990;Mothet et al, 2000;Billups and Attwell, 2003;Boehning and Snyder, 2003). Immunoreactivity for D-serine and its synthetic enzyme is predominantly limited to glial cells in brain (Schell et al, 1995;Wolosker et al, 1999), and astroglia (astrocytes) are capable of regulated Ca 21 -dependent D-serine release (Mothet et al, 2005) proximal to neuronal NMDA receptors in quantities sufficient to influence neuronal function, development, and survival (Schell et al, 1997;Yang et al, 2003;Katsuki et al, 2004;Kim et al, 2005;Shleper et al, 2005;Panatier et al, 2006).…”

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confidence: 98%

Functional and immunocytochemical characterization of D‐serine transporters in cortical neuron and astrocyte cultures

Shao¹,

Kamboj²,

Anderson³

2009

J of Neuroscience Research

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D-serine is an endogenous coagonist of N-methyl-D-aspartate (NMDA) receptors that plays an important role in synaptic function, neuronal development, and excitotoxicity. Mechanisms of D-serine transport are important in regulation of extracellular D-serine concentration and therefore of these critical processes. D-serine can be transported with low affinity through the Na(+)-dependent amino acid transporter termed ASCT2, whereas high-affinity D-serine uptake has been reported through the Na(+)-independent transporter termed asc-1. We investigated immunoreactivity for ASCT2 and asc-1 and D-serine transport kinetics in cultured cortical neurons and astrocytes to gain insight into how D-serine transporters regulate CNS D-serine levels. Both neurons and astrocytes exhibited low-affinity Na(+)-dependent D-serine uptake (K(T) > 1 mM) with broad substrate selectivity that was consistent with uptake through ASCT2. Both neurons and astrocytes also stained positively for ASCT2 in immunocytochemistry studies. Neurons but not astrocytes stained positively for the high-affinity D-serine transporter asc-1, but no evidence of functional asc-1 could be detected in neurons with conditions that produced such activity in cortical synaptosomes. These data support ASCT2 function in both neuron and astrocyte cultures and identify a discrepancy between observed asc-1 immunoreactivity and lack of functional asc-1 activity in neuron cultures. Together these findings further our knowledge of the processes that govern D-serine regulation.

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“…Finally, NMDA receptors play an important role in the excitability of granule cells . While binding of glycine to its allosteric site on the NMDA receptors could potentiate mossy fiber to granule cell transmission, the glycine site appears to be saturated under basal conditions (Billups and Attwell 2003). More studies are needed to understand the functional impact of Golgi cells heterogeneity, with regard to their transmitter phenotype and to the expression of functional markers, on granule cell layer information processing.…”

Section: Golgi Cells Are a Neurochemically Heterogenous Group Of Cellsmentioning

confidence: 98%

Golgi Neurons

Pietrajtis

Dieudonné

2013

Handbook of the Cerebellum and Cerebellar Disorders

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The Golgi cell is an essential cellular component of the cerebellar cortex and the only source of inhibition to the billions of granule cells forming the cortical input layer. While considered as a single neuronal class, separate from Lugaro cells, Golgi cells form a highly heterogeneous population, both morphologically and immunohistochemically. Golgi cells are interconnected by electrical synapses and connected to other cortical cell types by chemical synapses, forming feedforward and feedback inhibitory loops onto granule cells. Golgi cells are thus ideally placed to control the gain and temporal pattern of granule cell discharge in response to afferent mossy fiber activity.In vivo Golgi cells fire irregularly and respond to peripheral stimuli with brief burst responses or prolonged pauses. In the behaving animal, the firing rate of Golgi cells is modulated and forms sensory-motor receptive fields. Furthermore, Golgi cell activity is coordinated with local field potential oscillations in the beta range both locally and along the parallel fiber beams. Detailed computer models have been generated and predict complex oscillatory behaviors of the granule cell layer network at various frequencies. The impact of these oscillations on the encoding capacity of the granular layer is still debated, and further recordings are needed to understand how Golgi cells affect granule cell spike timing.

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Active release of glycine or d‐serine saturates the glycine site of NMDA receptors at the cerebellar mossy fibre to granule cell synapse

Cited by 36 publications

References 46 publications

D-Serine Augments NMDA-NR2B Receptor-Dependent Hippocampal Long-Term Depression and Spatial Reversal Learning

D-Serine Augments NMDA-NR2B Receptor-Dependent Hippocampal Long-Term Depression and Spatial Reversal Learning

Functional and immunocytochemical characterization of D‐serine transporters in cortical neuron and astrocyte cultures

Golgi Neurons

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