Astrocytes Release D-serine by a Large Vesicle

Overview

Journal Neuroscience

Specialty Neurology

Date 2013 Mar 15

PMID 23485803

Citations 29

Authors

N Kang

H Peng

Y Yu

P K Stanton

T R Guilarte

J Kang

Affiliations

Soon will be listed here.

Abstract

Long-term potentiation (LTP) of synaptic transmission in the CA1 region of the hippocampus depends on the activation of N-methyl-D-aspartate receptors (NMDARs), which can be regulated by Ca²⁺-dependent release of D-serine from astrocytes. The detailed mechanism underlying astrocytic d-serine release is still unknown. In hippocampal slices prepared from Sprague-Dawley rats, we found that clamping astrocytic [Ca²⁺] at 100-150 nM or puffing artificial cerebrospinal fluid (ACSF) into the extracellular space (weak mechanical stimulation) enhanced the synaptic activation of NMDARs. The enhancement was blocked by the NMDAR glycine site antagonist 5,7-dichlorokynurenic acid, glycine saturation, and infusion of astrocytes with D-amino acid oxidase and the serine racemase inhibitor L-erythro-3-hydroxyaspartate, suggesting the involvement of astrocytic D-serine release. Intracellular 100-150 nM [Ca²⁺] or puffing ACSF stimulated astrocytes to generate D-serine-containing large vesicles (1-3 μm), exocytotic fusion of which released D-serine. The formation of astrocytic large vesicles involved the intracellular fusion of small vesicles and/or other organelles. Spontaneous fusion of large vesicles occurred occasionally in astrocytes at rest, contributing to baseline D-serine levels, which increased the rising slope of NMDAR post-burst potentiation (PBP) without altering the PBP peak amplitude. Thus, under physiological conditions, astrocytic D-serine release by large vesicles facilitated weak theta-burst (TBS consisting of five bursts), but not strong TBS (TBS consisting of 10 bursts) stimulation-induced LTP.

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References

Agulhon C, Petravicz J, McMullen A, Sweger E, Minton S, Taves S . What is the role of astrocyte calcium in neurophysiology?. Neuron. 2008; 59(6):932-46. PMC: 3623689. DOI: 10.1016/j.neuron.2008.09.004. View

Schell M, Molliver M, Snyder S . D-serine, an endogenous synaptic modulator: localization to astrocytes and glutamate-stimulated release. Proc Natl Acad Sci U S A. 1995; 92(9):3948-52. PMC: 42079. DOI: 10.1073/pnas.92.9.3948. View

Williams S, Diaz C, Macnab L, Sullivan R, Pow D . Immunocytochemical analysis of D-serine distribution in the mammalian brain reveals novel anatomical compartmentalizations in glia and neurons. Glia. 2005; 53(4):401-11. DOI: 10.1002/glia.20300. View

Fellin T, Pascual O, Gobbo S, Pozzan T, Haydon P, Carmignoto G . Neuronal synchrony mediated by astrocytic glutamate through activation of extrasynaptic NMDA receptors. Neuron. 2004; 43(5):729-43. DOI: 10.1016/j.neuron.2004.08.011. View

Steinhauser C, Jabs R, Kettenmann H . Properties of GABA and glutamate responses in identified glial cells of the mouse hippocampal slice. Hippocampus. 1994; 4(1):19-35. DOI: 10.1002/hipo.450040105. View

Xu J, Peng H, Kang N, Zhao Z, Lin J, Stanton P . Glutamate-induced exocytosis of glutamate from astrocytes. J Biol Chem. 2007; 282(33):24185-97. DOI: 10.1074/jbc.M700452200. View

Fratti R, Jun Y, Merz A, Margolis N, Wickner W . Interdependent assembly of specific regulatory lipids and membrane fusion proteins into the vertex ring domain of docked vacuoles. J Cell Biol. 2004; 167(6):1087-98. PMC: 2172599. DOI: 10.1083/jcb.200409068. View

Milner B, Squire L, Kandel E . Cognitive neuroscience and the study of memory. Neuron. 1998; 20(3):445-68. DOI: 10.1016/s0896-6273(00)80987-3. View

Muller D, Nikonenko I, Jourdain P, Alberi S . LTP, memory and structural plasticity. Curr Mol Med. 2002; 2(7):605-11. DOI: 10.2174/1566524023362041. View

10.

Xie X, Barrionuevo G, Berger T . Differential expression of short-term potentiation by AMPA and NMDA receptors in dentate gyrus. Learn Mem. 1996; 3(2-3):115-23. DOI: 10.1101/lm.3.2-3.115. View

11.

Panatier A, Vallee J, Haber M, Murai K, Lacaille J, Robitaille R . Astrocytes are endogenous regulators of basal transmission at central synapses. Cell. 2011; 146(5):785-98. DOI: 10.1016/j.cell.2011.07.022. View

12.

Liu Q, Xu Q, Arcuino G, Kang J, Nedergaard M . Astrocyte-mediated activation of neuronal kainate receptors. Proc Natl Acad Sci U S A. 2004; 101(9):3172-7. PMC: 365762. DOI: 10.1073/pnas.0306731101. View

13.

Whitlock J, Heynen A, Shuler M, Bear M . Learning induces long-term potentiation in the hippocampus. Science. 2006; 313(5790):1093-7. DOI: 10.1126/science.1128134. View

14.

Agulhon C, Fiacco T, McCarthy K . Hippocampal short- and long-term plasticity are not modulated by astrocyte Ca2+ signaling. Science. 2010; 327(5970):1250-4. DOI: 10.1126/science.1184821. View

15.

Petravicz J, Fiacco T, McCarthy K . Loss of IP3 receptor-dependent Ca2+ increases in hippocampal astrocytes does not affect baseline CA1 pyramidal neuron synaptic activity. J Neurosci. 2008; 28(19):4967-73. PMC: 2709811. DOI: 10.1523/JNEUROSCI.5572-07.2008. View

16.

Balan L, Foltyn V, Zehl M, Dumin E, Dikopoltsev E, Knoh D . Feedback inactivation of D-serine synthesis by NMDA receptor-elicited translocation of serine racemase to the membrane. Proc Natl Acad Sci U S A. 2009; 106(18):7589-94. PMC: 2678608. DOI: 10.1073/pnas.0809442106. View

17.

Kang J, Jiang L, Goldman S, Nedergaard M . Astrocyte-mediated potentiation of inhibitory synaptic transmission. Nat Neurosci. 1999; 1(8):683-92. DOI: 10.1038/3684. View

18.

Charles A, Merrill J, DIRKSEN E, Sanderson M . Intercellular signaling in glial cells: calcium waves and oscillations in response to mechanical stimulation and glutamate. Neuron. 1991; 6(6):983-92. DOI: 10.1016/0896-6273(91)90238-u. View

19.

Bliss T, Collingridge G . A synaptic model of memory: long-term potentiation in the hippocampus. Nature. 1993; 361(6407):31-9. DOI: 10.1038/361031a0. View

20.

Shigetomi E, Bowser D, Sofroniew M, Khakh B . Two forms of astrocyte calcium excitability have distinct effects on NMDA receptor-mediated slow inward currents in pyramidal neurons. J Neurosci. 2008; 28(26):6659-63. PMC: 2866443. DOI: 10.1523/JNEUROSCI.1717-08.2008. View