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. 1995 Jan 15;482(Pt 2):325–352. doi: 10.1113/jphysiol.1995.sp020521

Dendritic glutamate receptor channels in rat hippocampal CA3 and CA1 pyramidal neurons.

N Spruston 1, P Jonas 1, B Sakmann 1
PMCID: PMC1157732  PMID: 7536248

Abstract

1. Properties of dendritic glutamate receptor (GluR) channels were investigated using fast application of glutamate to outside-out membrane patches isolated from the apical dendrites of CA3 and CA1 pyramidal neurons in rat hippocampal slices. CA3 patches were formed (15-76 microns from the soma) in the region of mossy fibre (MF) synapses, and CA1 patches (25-174 microns from the soma) in the region of Schaffer collateral (SC) innervation. 2. Dual-component responses consisting of a rapidly rising and decaying component followed by a second, substantially slower, component were elicited by 1 ms pulses of 1 mM glutamate in the presence of 10 microM glycine and absence of external Mg2+. The fast component was selectively blocked by 2-5 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and the slow component by 30 microM D-2-amino-5-phosphonopentanoic acid (D-AP5), suggesting that the fast and slow components were mediated by the GluR channels of the L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and NMDA type, respectively. The peak amplitude ratio of the NMDA to AMPA receptor-mediated components varied between 0.03 and 0.62 in patches from both CA3 and CA1 dendrites. Patches lacking either component were rarely observed. 3. The peak current-voltage (I-V) relationship of the fast component was almost linear, whereas the I-V relationship of the slow component showed a region of negative slope in the presence of 1 mM external Mg2+. The reversal potential for both components was close to 0 mV. 4. Kainate-preferring GluR channels did not contribute appreciably to the response to glutamate. The responses to 100 ms pulses of 1 mM glutamate were mimicked by application of 1 mM AMPA, whereas 1 mM kainate produced much smaller, weakly desensitizing currents. This suggests that the fast component is primarily mediated by the action of glutamate on AMPA-preferring receptors. 5. The mean elementary conductance of AMPA receptor channels was about 10 pS, as estimated by non-stationary fluctuation analysis. The permeability of these channels to Ca2+ was low (approximately 5% of the permeability to Cs+). 6. The elementary conductance of NMDA receptor channels was larger, with a main conductance state of about 45 pS. These channels were 3.6 times more permeable to Ca2+ than to Cs+.(ABSTRACT TRUNCATED AT 400 WORDS)

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ascher P., Nowak L. The role of divalent cations in the N-methyl-D-aspartate responses of mouse central neurones in culture. J Physiol. 1988 May;399:247–266. doi: 10.1113/jphysiol.1988.sp017078. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Assaf S. Y., Chung S. H. Release of endogenous Zn2+ from brain tissue during activity. Nature. 1984 Apr 19;308(5961):734–736. doi: 10.1038/308734a0. [DOI] [PubMed] [Google Scholar]
  3. Bekkers J. M., Stevens C. F. NMDA and non-NMDA receptors are co-localized at individual excitatory synapses in cultured rat hippocampus. Nature. 1989 Sep 21;341(6239):230–233. doi: 10.1038/341230a0. [DOI] [PubMed] [Google Scholar]
  4. Benke T. A., Jones O. T., Collingridge G. L., Angelides K. J. N-Methyl-D-aspartate receptors are clustered and immobilized on dendrites of living cortical neurons. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7819–7823. doi: 10.1073/pnas.90.16.7819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bliss T. V., Collingridge G. L. A synaptic model of memory: long-term potentiation in the hippocampus. Nature. 1993 Jan 7;361(6407):31–39. doi: 10.1038/361031a0. [DOI] [PubMed] [Google Scholar]
  6. Carmignoto G., Vicini S. Activity-dependent decrease in NMDA receptor responses during development of the visual cortex. Science. 1992 Nov 6;258(5084):1007–1011. doi: 10.1126/science.1279803. [DOI] [PubMed] [Google Scholar]
  7. Clements J. D., Lester R. A., Tong G., Jahr C. E., Westbrook G. L. The time course of glutamate in the synaptic cleft. Science. 1992 Nov 27;258(5087):1498–1501. doi: 10.1126/science.1359647. [DOI] [PubMed] [Google Scholar]
  8. Colquhoun D., Jonas P., Sakmann B. Action of brief pulses of glutamate on AMPA/kainate receptors in patches from different neurones of rat hippocampal slices. J Physiol. 1992 Dec;458:261–287. doi: 10.1113/jphysiol.1992.sp019417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cull-Candy S. G., Howe J. R., Ogden D. C. Noise and single channels activated by excitatory amino acids in rat cerebellar granule neurones. J Physiol. 1988 Jun;400:189–222. doi: 10.1113/jphysiol.1988.sp017117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Edmonds B., Colquhoun D. Rapid decay of averaged single-channel NMDA receptor activations recorded at low agonist concentration. Proc Biol Sci. 1992 Dec 22;250(1329):279–286. doi: 10.1098/rspb.1992.0160. [DOI] [PubMed] [Google Scholar]
  11. Forsythe I. D., Westbrook G. L. Slow excitatory postsynaptic currents mediated by N-methyl-D-aspartate receptors on cultured mouse central neurones. J Physiol. 1988 Feb;396:515–533. doi: 10.1113/jphysiol.1988.sp016975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gibb A. J., Colquhoun D. Activation of N-methyl-D-aspartate receptors by L-glutamate in cells dissociated from adult rat hippocampus. J Physiol. 1992 Oct;456:143–179. doi: 10.1113/jphysiol.1992.sp019331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hessler N. A., Shirke A. M., Malinow R. The probability of transmitter release at a mammalian central synapse. Nature. 1993 Dec 9;366(6455):569–572. doi: 10.1038/366569a0. [DOI] [PubMed] [Google Scholar]
  14. Hestrin S. Developmental regulation of NMDA receptor-mediated synaptic currents at a central synapse. Nature. 1992 Jun 25;357(6380):686–689. doi: 10.1038/357686a0. [DOI] [PubMed] [Google Scholar]
  15. Hestrin S. Different glutamate receptor channels mediate fast excitatory synaptic currents in inhibitory and excitatory cortical neurons. Neuron. 1993 Dec;11(6):1083–1091. doi: 10.1016/0896-6273(93)90221-c. [DOI] [PubMed] [Google Scholar]
  16. Hestrin S., Nicoll R. A., Perkel D. J., Sah P. Analysis of excitatory synaptic action in pyramidal cells using whole-cell recording from rat hippocampal slices. J Physiol. 1990 Mar;422:203–225. doi: 10.1113/jphysiol.1990.sp017980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hestrin S., Sah P., Nicoll R. A. Mechanisms generating the time course of dual component excitatory synaptic currents recorded in hippocampal slices. Neuron. 1990 Sep;5(3):247–253. doi: 10.1016/0896-6273(90)90162-9. [DOI] [PubMed] [Google Scholar]
  18. Howell G. A., Welch M. G., Frederickson C. J. Stimulation-induced uptake and release of zinc in hippocampal slices. Nature. 1984 Apr 19;308(5961):736–738. doi: 10.1038/308736a0. [DOI] [PubMed] [Google Scholar]
  19. Iino M., Ozawa S., Tsuzuki K. Permeation of calcium through excitatory amino acid receptor channels in cultured rat hippocampal neurones. J Physiol. 1990 May;424:151–165. doi: 10.1113/jphysiol.1990.sp018060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Jaffe D. B., Johnston D., Lasser-Ross N., Lisman J. E., Miyakawa H., Ross W. N. The spread of Na+ spikes determines the pattern of dendritic Ca2+ entry into hippocampal neurons. Nature. 1992 May 21;357(6375):244–246. doi: 10.1038/357244a0. [DOI] [PubMed] [Google Scholar]
  21. Jahr C. E. High probability opening of NMDA receptor channels by L-glutamate. Science. 1992 Jan 24;255(5043):470–472. doi: 10.1126/science.1346477. [DOI] [PubMed] [Google Scholar]
  22. Jahr C. E., Stevens C. F. Glutamate activates multiple single channel conductances in hippocampal neurons. Nature. 1987 Feb 5;325(6104):522–525. doi: 10.1038/325522a0. [DOI] [PubMed] [Google Scholar]
  23. Johnston D., Brown T. H. Interpretation of voltage-clamp measurements in hippocampal neurons. J Neurophysiol. 1983 Aug;50(2):464–486. doi: 10.1152/jn.1983.50.2.464. [DOI] [PubMed] [Google Scholar]
  24. Johnston D., Williams S., Jaffe D., Gray R. NMDA-receptor-independent long-term potentiation. Annu Rev Physiol. 1992;54:489–505. doi: 10.1146/annurev.ph.54.030192.002421. [DOI] [PubMed] [Google Scholar]
  25. Jonas P., Major G., Sakmann B. Quantal components of unitary EPSCs at the mossy fibre synapse on CA3 pyramidal cells of rat hippocampus. J Physiol. 1993 Dec;472:615–663. doi: 10.1113/jphysiol.1993.sp019965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Jonas P., Racca C., Sakmann B., Seeburg P. H., Monyer H. Differences in Ca2+ permeability of AMPA-type glutamate receptor channels in neocortical neurons caused by differential GluR-B subunit expression. Neuron. 1994 Jun;12(6):1281–1289. doi: 10.1016/0896-6273(94)90444-8. [DOI] [PubMed] [Google Scholar]
  27. Jonas P., Spruston N. Mechanisms shaping glutamate-mediated excitatory postsynaptic currents in the CNS. Curr Opin Neurobiol. 1994 Jun;4(3):366–372. doi: 10.1016/0959-4388(94)90098-1. [DOI] [PubMed] [Google Scholar]
  28. Keller B. U., Konnerth A., Yaari Y. Patch clamp analysis of excitatory synaptic currents in granule cells of rat hippocampus. J Physiol. 1991 Apr;435:275–293. doi: 10.1113/jphysiol.1991.sp018510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Legendre P., Westbrook G. L. The inhibition of single N-methyl-D-aspartate-activated channels by zinc ions on cultured rat neurones. J Physiol. 1990 Oct;429:429–449. doi: 10.1113/jphysiol.1990.sp018266. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Lerma J., Paternain A. V., Naranjo J. R., Mellström B. Functional kainate-selective glutamate receptors in cultured hippocampal neurons. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11688–11692. doi: 10.1073/pnas.90.24.11688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Lester R. A., Clements J. D., Westbrook G. L., Jahr C. E. Channel kinetics determine the time course of NMDA receptor-mediated synaptic currents. Nature. 1990 Aug 9;346(6284):565–567. doi: 10.1038/346565a0. [DOI] [PubMed] [Google Scholar]
  32. Lester R. A., Tong G., Jahr C. E. Interactions between the glycine and glutamate binding sites of the NMDA receptor. J Neurosci. 1993 Mar;13(3):1088–1096. doi: 10.1523/JNEUROSCI.13-03-01088.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. McBain C., Dingledine R. Dual-component miniature excitatory synaptic currents in rat hippocampal CA3 pyramidal neurons. J Neurophysiol. 1992 Jul;68(1):16–27. doi: 10.1152/jn.1992.68.1.16. [DOI] [PubMed] [Google Scholar]
  34. Miyakawa H., Ross W. N., Jaffe D., Callaway J. C., Lasser-Ross N., Lisman J. E., Johnston D. Synaptically activated increases in Ca2+ concentration in hippocampal CA1 pyramidal cells are primarily due to voltage-gated Ca2+ channels. Neuron. 1992 Dec;9(6):1163–1173. doi: 10.1016/0896-6273(92)90074-n. [DOI] [PubMed] [Google Scholar]
  35. Monaghan D. T., Holets V. R., Toy D. W., Cotman C. W. Anatomical distributions of four pharmacologically distinct 3H-L-glutamate binding sites. Nature. 1983 Nov 10;306(5939):176–179. doi: 10.1038/306176a0. [DOI] [PubMed] [Google Scholar]
  36. Monyer H., Burnashev N., Laurie D. J., Sakmann B., Seeburg P. H. Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron. 1994 Mar;12(3):529–540. doi: 10.1016/0896-6273(94)90210-0. [DOI] [PubMed] [Google Scholar]
  37. Nowak L. M., Wright J. M. Slow voltage-dependent changes in channel open-state probability underlie hysteresis of NMDA responses in Mg(2+)-free solutions. Neuron. 1992 Jan;8(1):181–187. doi: 10.1016/0896-6273(92)90119-x. [DOI] [PubMed] [Google Scholar]
  38. Nowak L., Bregestovski P., Ascher P., Herbet A., Prochiantz A. Magnesium gates glutamate-activated channels in mouse central neurones. Nature. 1984 Feb 2;307(5950):462–465. doi: 10.1038/307462a0. [DOI] [PubMed] [Google Scholar]
  39. Patneau D. K., Vyklicky L., Jr, Mayer M. L. Hippocampal neurons exhibit cyclothiazide-sensitive rapidly desensitizing responses to kainate. J Neurosci. 1993 Aug;13(8):3496–3509. doi: 10.1523/JNEUROSCI.13-08-03496.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Pérez-Clausell J., Danscher G. Intravesicular localization of zinc in rat telencephalic boutons. A histochemical study. Brain Res. 1985 Jun 24;337(1):91–98. doi: 10.1016/0006-8993(85)91612-9. [DOI] [PubMed] [Google Scholar]
  41. Rosenmund C., Clements J. D., Westbrook G. L. Nonuniform probability of glutamate release at a hippocampal synapse. Science. 1993 Oct 29;262(5134):754–757. doi: 10.1126/science.7901909. [DOI] [PubMed] [Google Scholar]
  42. Sather W., Dieudonné S., MacDonald J. F., Ascher P. Activation and desensitization of N-methyl-D-aspartate receptors in nucleated outside-out patches from mouse neurones. J Physiol. 1992 May;450:643–672. doi: 10.1113/jphysiol.1992.sp019148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Schneggenburger R., Zhou Z., Konnerth A., Neher E. Fractional contribution of calcium to the cation current through glutamate receptor channels. Neuron. 1993 Jul;11(1):133–143. doi: 10.1016/0896-6273(93)90277-x. [DOI] [PubMed] [Google Scholar]
  44. Sigworth F. J. The variance of sodium current fluctuations at the node of Ranvier. J Physiol. 1980 Oct;307:97–129. doi: 10.1113/jphysiol.1980.sp013426. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Silver R. A., Traynelis S. F., Cull-Candy S. G. Rapid-time-course miniature and evoked excitatory currents at cerebellar synapses in situ. Nature. 1992 Jan 9;355(6356):163–166. doi: 10.1038/355163a0. [DOI] [PubMed] [Google Scholar]
  46. Spruston N., Jaffe D. B., Williams S. H., Johnston D. Voltage- and space-clamp errors associated with the measurement of electrotonically remote synaptic events. J Neurophysiol. 1993 Aug;70(2):781–802. doi: 10.1152/jn.1993.70.2.781. [DOI] [PubMed] [Google Scholar]
  47. Stern P., Béhé P., Schoepfer R., Colquhoun D. Single-channel conductances of NMDA receptors expressed from cloned cDNAs: comparison with native receptors. Proc Biol Sci. 1992 Dec 22;250(1329):271–277. doi: 10.1098/rspb.1992.0159. [DOI] [PubMed] [Google Scholar]
  48. Stern P., Edwards F. A., Sakmann B. Fast and slow components of unitary EPSCs on stellate cells elicited by focal stimulation in slices of rat visual cortex. J Physiol. 1992 Apr;449:247–278. doi: 10.1113/jphysiol.1992.sp019085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Stuart G. J., Dodt H. U., Sakmann B. Patch-clamp recordings from the soma and dendrites of neurons in brain slices using infrared video microscopy. Pflugers Arch. 1993 Jun;423(5-6):511–518. doi: 10.1007/BF00374949. [DOI] [PubMed] [Google Scholar]
  50. Stuart G. J., Sakmann B. Active propagation of somatic action potentials into neocortical pyramidal cell dendrites. Nature. 1994 Jan 6;367(6458):69–72. doi: 10.1038/367069a0. [DOI] [PubMed] [Google Scholar]
  51. Traynelis S. F., Silver R. A., Cull-Candy S. G. Estimated conductance of glutamate receptor channels activated during EPSCs at the cerebellar mossy fiber-granule cell synapse. Neuron. 1993 Aug;11(2):279–289. doi: 10.1016/0896-6273(93)90184-s. [DOI] [PubMed] [Google Scholar]
  52. Wisden W., Seeburg P. H. Mammalian ionotropic glutamate receptors. Curr Opin Neurobiol. 1993 Jun;3(3):291–298. doi: 10.1016/0959-4388(93)90120-n. [DOI] [PubMed] [Google Scholar]
  53. Woodhull A. M. Ionic blockage of sodium channels in nerve. J Gen Physiol. 1973 Jun;61(6):687–708. doi: 10.1085/jgp.61.6.687. [DOI] [PMC free article] [PubMed] [Google Scholar]

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