Homeostatic Regulation of Synaptic GlyR Numbers Driven by Lateral Diffusion

Sabine Lévi; Claude Schweizer; Hiroko Bannai; Olivier Pascual; Cécile Charrier; Antoine Triller

doi:10.1016/j.neuron.2008.05.030

Homeostatic Regulation of Synaptic GlyR Numbers Driven by Lateral Diffusion

Sabine Lévi, Claude Schweizer, Hiroko Bannai, Olivier Pascual, Cécile Charrier, Antoine Triller^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

45 Citations (Scopus)

Abstract

In the spinal cord, most inhibitory synapses have a mixed glycine-GABA phenotype. Using a pharmacological approach, we report an NMDAR activity-dependent regulation of the mobility of GlyRs but not GABA_ARs at inhibitory synapses in cultured rat spinal cord neurons. The NMDAR-induced decrease in GlyR lateral diffusion was correlated with an increase in receptor cluster number and glycinergic mIPSC amplitude. Changes in GlyR diffusion properties occurred rapidly and before the changes in the number of synaptic receptors. Regulation of synaptic GlyR content occurred without change in the amount of gephyrin. Moreover, NMDAR-dependent regulation of GlyR lateral diffusion required calcium influx and calcium release from stores. Therefore, excitation may increase GlyR levels at synapses by a calcium-mediated increase in postsynaptic GlyR trapping involving regulation of receptor-scaffold interactions. This provides a mechanism for a rapid homeostatic regulation of the inhibitory glycinergic component at mixed glycine-GABA synapses in response to increased NMDA excitatory transmission.

Original language	English
Pages (from-to)	261-273
Number of pages	13
Journal	Neuron
Volume	59
Issue number	2
DOIs	https://doi.org/10.1016/j.neuron.2008.05.030
Publication status	Published - 2008 Jul 31
Externally published	Yes

Keywords

CELLBIO
MOLIMMUNO
SIGNALING

ASJC Scopus subject areas

Neuroscience(all)

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10.1016/j.neuron.2008.05.030

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@article{323c55659a0949c4a1c5ad8b617773b5,

title = "Homeostatic Regulation of Synaptic GlyR Numbers Driven by Lateral Diffusion",

abstract = "In the spinal cord, most inhibitory synapses have a mixed glycine-GABA phenotype. Using a pharmacological approach, we report an NMDAR activity-dependent regulation of the mobility of GlyRs but not GABAARs at inhibitory synapses in cultured rat spinal cord neurons. The NMDAR-induced decrease in GlyR lateral diffusion was correlated with an increase in receptor cluster number and glycinergic mIPSC amplitude. Changes in GlyR diffusion properties occurred rapidly and before the changes in the number of synaptic receptors. Regulation of synaptic GlyR content occurred without change in the amount of gephyrin. Moreover, NMDAR-dependent regulation of GlyR lateral diffusion required calcium influx and calcium release from stores. Therefore, excitation may increase GlyR levels at synapses by a calcium-mediated increase in postsynaptic GlyR trapping involving regulation of receptor-scaffold interactions. This provides a mechanism for a rapid homeostatic regulation of the inhibitory glycinergic component at mixed glycine-GABA synapses in response to increased NMDA excitatory transmission.",

keywords = "CELLBIO, MOLIMMUNO, SIGNALING",

author = "Sabine L{\'e}vi and Claude Schweizer and Hiroko Bannai and Olivier Pascual and C{\'e}cile Charrier and Antoine Triller",

note = "Funding Information: We thank B. Barbour (ENS, Paris, France) for critical reading of the manuscript. The authors are thankful to B. Riveau and C. Ribrault for the supply of primary cultures of spinal cord neurons. We thank J.-M. Fritschy (University of Zurich, Switzerland) for guinea pig γ2 antibody, B. Gasnier (IBPC, Paris, France) for VIAAT antibody, R.-M. M{\`e}ge (IFM, Paris, France) for N-Cam antibody, and K. Mikoshiba (RIKEN, Japan) for 2-APB. We thank M. Dahan (ENS, Paris, France) and T. Inoue (University of Tokyo, Japan) for the use of their SPT and calcium imaging programs, respectively. This work was supported by the Institut National de la Science et de la Recherche M{\'e}dicale, the Minist{\`e}re de la Recherche, the Institut de Recherche sur la Moelle Epini{\`e}re, the ACI BDP0235, the Sesame convention E. 1762 R{\'e}gion Ile de France, and the Agence Nationale de la Recherche ANR-05-NEUR-043-02. H.B. was supported by Toyobo Biotechnology Foundation, Hayashi Memorial Foundation for Female Natural Scientists, and The Japan Society for the Promotion of Science. ",

year = "2008",

month = jul,

day = "31",

doi = "10.1016/j.neuron.2008.05.030",

language = "English",

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journal = "Neuron",

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T1 - Homeostatic Regulation of Synaptic GlyR Numbers Driven by Lateral Diffusion

AU - Lévi, Sabine

AU - Schweizer, Claude

AU - Bannai, Hiroko

AU - Pascual, Olivier

AU - Charrier, Cécile

AU - Triller, Antoine

N1 - Funding Information: We thank B. Barbour (ENS, Paris, France) for critical reading of the manuscript. The authors are thankful to B. Riveau and C. Ribrault for the supply of primary cultures of spinal cord neurons. We thank J.-M. Fritschy (University of Zurich, Switzerland) for guinea pig γ2 antibody, B. Gasnier (IBPC, Paris, France) for VIAAT antibody, R.-M. Mège (IFM, Paris, France) for N-Cam antibody, and K. Mikoshiba (RIKEN, Japan) for 2-APB. We thank M. Dahan (ENS, Paris, France) and T. Inoue (University of Tokyo, Japan) for the use of their SPT and calcium imaging programs, respectively. This work was supported by the Institut National de la Science et de la Recherche Médicale, the Ministère de la Recherche, the Institut de Recherche sur la Moelle Epinière, the ACI BDP0235, the Sesame convention E. 1762 Région Ile de France, and the Agence Nationale de la Recherche ANR-05-NEUR-043-02. H.B. was supported by Toyobo Biotechnology Foundation, Hayashi Memorial Foundation for Female Natural Scientists, and The Japan Society for the Promotion of Science.

PY - 2008/7/31

Y1 - 2008/7/31

N2 - In the spinal cord, most inhibitory synapses have a mixed glycine-GABA phenotype. Using a pharmacological approach, we report an NMDAR activity-dependent regulation of the mobility of GlyRs but not GABAARs at inhibitory synapses in cultured rat spinal cord neurons. The NMDAR-induced decrease in GlyR lateral diffusion was correlated with an increase in receptor cluster number and glycinergic mIPSC amplitude. Changes in GlyR diffusion properties occurred rapidly and before the changes in the number of synaptic receptors. Regulation of synaptic GlyR content occurred without change in the amount of gephyrin. Moreover, NMDAR-dependent regulation of GlyR lateral diffusion required calcium influx and calcium release from stores. Therefore, excitation may increase GlyR levels at synapses by a calcium-mediated increase in postsynaptic GlyR trapping involving regulation of receptor-scaffold interactions. This provides a mechanism for a rapid homeostatic regulation of the inhibitory glycinergic component at mixed glycine-GABA synapses in response to increased NMDA excitatory transmission.

AB - In the spinal cord, most inhibitory synapses have a mixed glycine-GABA phenotype. Using a pharmacological approach, we report an NMDAR activity-dependent regulation of the mobility of GlyRs but not GABAARs at inhibitory synapses in cultured rat spinal cord neurons. The NMDAR-induced decrease in GlyR lateral diffusion was correlated with an increase in receptor cluster number and glycinergic mIPSC amplitude. Changes in GlyR diffusion properties occurred rapidly and before the changes in the number of synaptic receptors. Regulation of synaptic GlyR content occurred without change in the amount of gephyrin. Moreover, NMDAR-dependent regulation of GlyR lateral diffusion required calcium influx and calcium release from stores. Therefore, excitation may increase GlyR levels at synapses by a calcium-mediated increase in postsynaptic GlyR trapping involving regulation of receptor-scaffold interactions. This provides a mechanism for a rapid homeostatic regulation of the inhibitory glycinergic component at mixed glycine-GABA synapses in response to increased NMDA excitatory transmission.

KW - CELLBIO

KW - MOLIMMUNO

KW - SIGNALING

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DO - 10.1016/j.neuron.2008.05.030

M3 - Article

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AN - SCOPUS:47749151041

SN - 0896-6273

VL - 59

SP - 261

EP - 273

JO - Neuron

JF - Neuron

IS - 2

ER -

Homeostatic Regulation of Synaptic GlyR Numbers Driven by Lateral Diffusion

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Keywords

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