QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, May 19, 2004, 24(20):4767-4777; doi:10.1523/JNEUROSCI.0364-04.2004

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (53) Citing Articles via Google Scholar Google Scholar Articles by Scimemi, A. Articles by Rusakov, D. A. Search for Related Content PubMed PubMed Citation Articles by Scimemi, A. Articles by Rusakov, D. A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB (L)-ASPARTIC ACID GLUTAMIC ACID HYDROCHLORIDE

 Previous Article  |  Next Article 

Cellular/Molecular
NR2B-Containing Receptors Mediate Cross Talk among Hippocampal Synapses

Annalisa Scimemi,¹ Alan Fine,² Dimitri M. Kullmann,¹ and Dmitri A. Rusakov¹

¹Institute of Neurology, University College London, London WC1N 3BG, United Kingdom, and ²Division of Neurophysiology, National Institute for Medical Research, London NW7 1AA, United Kingdom

Under some conditions, synaptically released glutamate can exert long-range actions in the cortical microcircuitry. To what extent glutamate spillover leads to direct cross talk among individual synapses remains unclear. We recorded NMDAR-mediated EPSCs in acute hippocampal slices at 35°C by stimulating two independent pathways that converge on the same CA1 pyramidal cell. Activation of a conditioning pathway in the presence of the use-dependent blocker dizocilpine maleate (MK801) resulted in partial NMDA receptor (NMDAR) blockade in the other, silent pathway. This was accompanied by an increase in the rise time of the EPSCs in the conditioning (although not the silent) pathway, implying an increase in diffusional distance from release site to NMDARs. We estimated that up to 30% of NMDARs contributing to EPSCs were activated by glutamate released from multiple synaptic sources; however, NMDAR-mediated synaptic cross talk was undetectable when NR2B subunit-containing receptors were blocked (but could be rescued by blocking glutamate uptake). We propose that NR2B-containing NMDARs can detect glutamate arising from multiple synapses, whereas NR2A-containing NMDARs only normally mediate direct synaptic transmission. These NMDAR isoforms thus play complementary roles in sensing global and local glutamate signals, respectively.

Key words: hippocampus; glutamate; spillover; NMDA receptors; NR2B; synapse

---

Received Feb 2, 2004; revised April 6, 2004; accepted April 6, 2004.

This article has been cited by other articles:

				F. Longordo, C. Kopp, M. Mishina, R. Lujan, and A. Luthi NR2A at CA1 Synapses Is Obligatory for the Susceptibility of Hippocampal Plasticity to Sleep Loss J. Neurosci., July 15, 2009; 29(28): 9026 - 9041. [Abstract] [Full Text] [PDF]

				T. Muller, D. Albrecht, and C. Gebhardt Both NR2A and NR2B subunits of the NMDA receptor are critical for long-term potentiation and long-term depression in the lateral amygdala of horizontal slices of adult mice Learn. Mem., May 27, 2009; 16(6): 395 - 405. [Abstract] [Full Text] [PDF]

				J. Zhang and J. S. Diamond Subunit- and Pathway-Specific Localization of NMDA Receptors and Scaffolding Proteins at Ganglion Cell Synapses in Rat Retina J. Neurosci., April 1, 2009; 29(13): 4274 - 4286. [Abstract] [Full Text] [PDF]

				D. R. Ireland and W. C. Abraham Mechanisms of Group I mGluR-Dependent Long-Term Depression of NMDA Receptor-Mediated Transmission at Schaffer Collateral-CA1 Synapses J Neurophysiol, March 1, 2009; 101(3): 1375 - 1385. [Abstract] [Full Text] [PDF]

				H. Wang, G. G. Stradtman III, X.-J. Wang, and W.-J. Gao A specialized NMDA receptor function in layer 5 recurrent microcircuitry of the adult rat prefrontal cortex PNAS, October 28, 2008; 105(43): 16791 - 16796. [Abstract] [Full Text] [PDF]

				J. Yang, S. E. L. Chamberlain, G. L. Woodhall, and R. S. G. Jones Mobility of NMDA autoreceptors but not postsynaptic receptors at glutamate synapses in the rat entorhinal cortex J. Physiol., October 15, 2008; 586(20): 4905 - 4924. [Abstract] [Full Text] [PDF]

				D. Atasoy, M. Ertunc, K. L. Moulder, J. Blackwell, C. Chung, J. Su, and E. T. Kavalali Spontaneous and Evoked Glutamate Release Activates Two Populations of NMDA Receptors with Limited Overlap J. Neurosci., October 1, 2008; 28(40): 10151 - 10166. [Abstract] [Full Text] [PDF]

				S. Sylantyev, L. P. Savtchenko, Y.-P. Niu, A. I. Ivanov, T. P. Jensen, D. M. Kullmann, M.-Y. Xiao, and D. A. Rusakov Electric Fields Due to Synaptic Currents Sharpen Excitatory Transmission Science, March 28, 2008; 319(5871): 1845 - 1849. [Abstract] [Full Text] [PDF]

				J. Zhao, Y. Peng, Z. Xu, R.-q. Chen, Q.-h. Gu, Z. Chen, and W. Lu Synaptic Metaplasticity through NMDA Receptor Lateral Diffusion J. Neurosci., March 19, 2008; 28(12): 3060 - 3070. [Abstract] [Full Text] [PDF]

				A. Z. Harris and D. L. Pettit Recruiting Extrasynaptic NMDA Receptors Augments Synaptic Signaling J Neurophysiol, February 1, 2008; 99(2): 524 - 533. [Abstract] [Full Text] [PDF]

				A. J. Milnerwood and L. A. Raymond Corticostriatal synaptic function in mouse models of Huntington's disease: early effects of huntingtin repeat length and protein load J. Physiol., December 15, 2007; 585(3): 817 - 831. [Abstract] [Full Text] [PDF]

				S. M. Logan, J. G. Partridge, J. A. Matta, A. Buonanno, and S. Vicini Long-Lasting NMDA Receptor-Mediated EPSCs in Mouse Striatal Medium Spiny Neurons J Neurophysiol, November 1, 2007; 98(5): 2693 - 2704. [Abstract] [Full Text] [PDF]

				A. Z. Harris and D. L. Pettit Extrasynaptic and synaptic NMDA receptors form stable and uniform pools in rat hippocampal slices J. Physiol., October 15, 2007; 584(2): 509 - 519. [Abstract] [Full Text] [PDF]

				S. Ding, T. Fellin, Y. Zhu, S.-Y. Lee, Y. P. Auberson, D. F. Meaney, D. A. Coulter, G. Carmignoto, and P. G. Haydon Enhanced Astrocytic Ca2+ Signals Contribute to Neuronal Excitotoxicity after Status Epilepticus J. Neurosci., October 3, 2007; 27(40): 10674 - 10684. [Abstract] [Full Text] [PDF]

				L. Sun and S. June Liu Activation of extrasynaptic NMDA receptors induces a PKC-dependent switch in AMPA receptor subtypes in mouse cerebellar stellate cells J. Physiol., September 1, 2007; 583(2): 537 - 553. [Abstract] [Full Text] [PDF]

				J. Glykys and I. Mody The main source of ambient GABA responsible for tonic inhibition in the mouse hippocampus J. Physiol., August 1, 2007; 582(3): 1163 - 1178. [Abstract] [Full Text] [PDF]

				K. L. Meur, M. Galante, M. C. Angulo, and E. Audinat Tonic activation of NMDA receptors by ambient glutamate of non-synaptic origin in the rat hippocampus J. Physiol., April 15, 2007; 580(2): 373 - 383. [Abstract] [Full Text] [PDF]

				C. Kopp, F. Longordo, J. R. Nicholson, and A. Luthi Insufficient Sleep Reversibly Alters Bidirectional Synaptic Plasticity and NMDA Receptor Function J. Neurosci., November 29, 2006; 26(48): 12456 - 12465. [Abstract] [Full Text] [PDF]

				P. G. Haydon and G. Carmignoto Astrocyte control of synaptic transmission and neurovascular coupling. Physiol Rev, July 1, 2006; 86(3): 1009 - 1031. [Abstract] [Full Text] [PDF]

				R. Scott and D. A. Rusakov Main determinants of presynaptic Ca2+ dynamics at individual mossy fiber-CA3 pyramidal cell synapses. J. Neurosci., June 28, 2006; 26(26): 7071 - 7081. [Abstract] [Full Text] [PDF]

				A. Ivanov, C. Pellegrino, S. Rama, I. Dumalska, Y. Salyha, Y. Ben-Ari, and I. Medina Opposing role of synaptic and extrasynaptic NMDA receptors in regulation of the extracellular signal-regulated kinases (ERK) activity in cultured rat hippocampal neurons J. Physiol., May 1, 2006; 572(3): 789 - 798. [Abstract] [Full Text] [PDF]

				A. Scimemi, S. Schorge, D. M. Kullmann, and M. C. Walker Epileptogenesis Is Associated With Enhanced Glutamatergic Transmission in the Perforant Path J Neurophysiol, February 1, 2006; 95(2): 1213 - 1220. [Abstract] [Full Text] [PDF]

				A. Sobczyk, V. Scheuss, and K. Svoboda NMDA Receptor Subunit-Dependent [Ca2+] Signaling in Individual Hippocampal Dendritic Spines J. Neurosci., June 29, 2005; 25(26): 6037 - 6046. [Abstract] [Full Text] [PDF]

				J. S. Diamond Deriving the Glutamate Clearance Time Course from Transporter Currents in CA1 Hippocampal Astrocytes: Transmitter Uptake Gets Faster during Development J. Neurosci., March 16, 2005; 25(11): 2906 - 2916. [Abstract] [Full Text] [PDF]

				S. G. Cull-Candy and D. N. Leszkiewicz Role of Distinct NMDA Receptor Subtypes at Central Synapses Sci. Signal., October 19, 2004; 2004(255): re16 - re16. [Abstract] [Full Text] [PDF]

				D. A. Rusakov, A. Scimemi, M. C. Walker, and D. M. Kullmann Comment on "Role of NMDA Receptor Subtypes in Governing the Direction of Hippocampal Synaptic Plasticity" Science, September 24, 2004; 305(5692): 1912b - 1912b. [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help