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PMID: 1972190 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Analysis of excitatory synaptic action in pyramidal cells using whole-cell recording from rat hippocampal slices.

The Journal of physiology ·Vol. 422 ·1990-03-00 ·Pages 203-25

Hestrin S, Nicoll RA, Perkel DJ, Sah P

Abstract

1. The pharmacological and biophysical properties of excitatory synapses in the CA1 region of the hippocampus were studied using patch electrodes and whole-cell recording from thin slices. 2. Excitatory postsynaptic currents (EPSCs) had a fast component whose amplitude was voltage insensitive and a slow component whose amplitude was voltage dependent with a region of negative slope resistance in the range of -70 to -30 mV. 3. The voltage-dependent component was abolished by the N-methyl-D-aspartate (NMDA) receptor antagonist DL-2-amino-5-phosphonovalerate (APV; 50 microM), which had no effect on the fast component. Conversely, the fast voltage-insensitive component was abolished by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 microM) which had no effect on the slow component. 4. In Ringer solution with no added Mg2+ the current-voltage relation of the NMDA component was linear over a much larger voltage range than in the presence of 1.3 mM-Mg2+. 5. The NMDA component of the EPSC could be switched off with a hyperpolarizing voltage step at the soma. The kinetics of this switch-off was used to estimate the speed of clamp control of the subsynaptic membrane as well as the electrotonic distance from the soma. The kinetic analysis of the EPSC was restricted to synapses which were judged to be under adequate voltage control. 6. For those synapses that were close to the soma the time constant for decay for the non-NMDA component, which was voltage insensitive, ranged from 4-8 ms. 7. The rise time for the NMDA component was 8-20 ms and the time constant for decay ranged from 60-150 ms. 8. During increased transmitter release with post-tetanic potentiation or application or phorbol esters, both components of the EPSC increased to a similar extent. 9. These experiments provide a detailed description of the dual receptor mechanism operating at hippocampal excitatory synapses. In addition, the experiments provide an electrophysiological method for estimating the electrotonic distance of synaptic inputs.

MeSH Terms
2-Amino-5-phosphonovalerate/pharmacology 6-Cyano-7-nitroquinoxaline-2,3-dione Action Potentials/drug effects Animals Hippocampus/physiology In Vitro Techniques Kinetics Magnesium/pharmacology Neurons/physiology Phorbol Esters/pharmacology Pyramidal Tracts/physiology Quinoxalines/pharmacology Rats Synapses/physiology
Chemicals
Phorbol Esters Quinoxalines phorbol-12,13-diacetate 6-Cyano-7-nitroquinoxaline-2,3-dione 2-Amino-5-phosphonovalerate Magnesium
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Hestrin S
Department of Physiology, University of California, San Francisco 94143.
Nicoll R A
Perkel D J
Sah P
References (53)
53 references, click to expand
  1. Slow excitatory postsynaptic currents mediated by N-methyl-D-aspartate receptors on cultured mouse central neurones.
    J Physiol. 1988 Feb;396:515-33 PMID: 2900892
  2. Excitatory amino acid transmitters.
    Annu Rev Pharmacol Toxicol. 1981;21:165-204 PMID: 6112965
  3. Intracellular fluoride alters the kinetic properties of calcium currents facilitating the investigation of synaptic events in hippocampal neurons.
    J Neurosci. 1986 Oct;6(10):2915-20 PMID: 2428953
  4. Ca2+-dependent and -independent release of neurotransmitters from PC12 cells: a role for protein kinase C activation?
    J Cell Biol. 1984 Aug;99(2):628-38 PMID: 6204995
  5. A thin slice preparation for patch clamp recordings from neurones of the mammalian central nervous system.
    Pflugers Arch. 1989 Sep;414(5):600-12 PMID: 2780225
  6. The synaptic current evoked in cat spinal motoneurones by impulses in single group 1a axons.
    J Physiol. 1983 Sep;342:615-32 PMID: 6313911
  7. Activation of protein kinase C augments evoked transmitter release.
    Nature. 1987 Jan 1-7;325(6099):58-60 PMID: 2432432
  8. N-methyl-D-aspartate-activated channels of mouse central neurones in magnesium-free solutions.
    J Physiol. 1988 May;399:207-26 PMID: 2457087
  9. CNQX blocks acidic amino acid induced depolarizations and synaptic components mediated by non-NMDA receptors in rat hippocampal slices.
    Neurosci Lett. 1988 Jun 29;89(2):182-6 PMID: 2899308
  10. Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones.
    Nature. 1984 May 17-23;309(5965):261-3 PMID: 6325946
  11. The effect of magnesium on the activity of motor nerve endings.
    J Physiol. 1954 Jun 28;124(3):553-9 PMID: 13175198
  12. On the kinetics of large-conductance glutamate-receptor ion channels in rat cerebellar granule neurons.
    Proc R Soc Lond B Biol Sci. 1988 May 23;233(1273):407-22 PMID: 2456583
  13. Excitation of hippocampal pyramidal cells by glutamate in the guinea-pig and rat.
    J Physiol. 1982 Apr;325:317-31 PMID: 7108779
  14. Contributions of quisqualate and NMDA receptors to the induction and expression of LTP.
    Science. 1988 Dec 23;242(4886):1694-7 PMID: 2904701
  15. Interaction of 6-cyano-7-nitroquinoxaline-2,3-dione with the N-methyl-D-aspartate receptor-associated glycine binding site.
    Mol Pharmacol. 1989 May;35(5):565-70 PMID: 2566902
  16. Phorbol ester and calcium act synergistically to enhance neurotransmitter release by brain neurons in culture.
    FEBS Lett. 1985 Jun 17;185(2):257-61 PMID: 2860013
  17. Excitatory amino acids in synaptic transmission in the Schaffer collateral-commissural pathway of the rat hippocampus.
    J Physiol. 1983 Jan;334:33-46 PMID: 6306230
  18. Noise and single channels activated by excitatory amino acids in rat cerebellar granule neurones.
    J Physiol. 1988 Jun;400:189-222 PMID: 2458453
  19. The physiology of excitatory amino acids in the vertebrate central nervous system.
    Prog Neurobiol. 1987;28(3):197-276 PMID: 2883706
  20. Effect of internal fluoride and phosphate on membrane currents during intracellular dialysis of nerve cells.
    Nature. 1975 Oct 23;257(5528):691-3 PMID: 1186845
  21. The distribution of [3H]kainate binding sites in primate hippocampus is similar to the distribution of both Ca2+-sensitive and Ca2+-insensitive [3H]kainate binding sites in rat hippocampus.
    Neurochem Res. 1986 Jul;11(7):1073-82 PMID: 3748275
  22. Diacylglycerol and phorbol ester stimulate secretion without raising cytoplasmic free calcium in human platelets.
    Nature. 1983 Sep 22-28;305(5932):317-9 PMID: 6621685
  23. Multiple-conductance channels activated by excitatory amino acids in cerebellar neurons.
    Nature. 1987 Feb 5-11;325(6104):525-8 PMID: 2433594
  24. Synaptic excitation in cultures of mouse spinal cord neurones: receptor pharmacology and behaviour of synaptic currents.
    J Physiol. 1986 Mar;372:169-90 PMID: 2873240
  25. Involvement of N-methyl-D-aspartate receptors in epileptiform bursting in the rat hippocampal slice.
    J Physiol. 1986 Nov;380:175-89 PMID: 2886653
  26. Interpretation of voltage-clamp measurements in hippocampal neurons.
    J Neurophysiol. 1983 Aug;50(2):464-86 PMID: 6310063
  27. Excitatory amino acid receptors in hippocampal neurons: kainate fails to desensitize them.
    Neurosci Lett. 1986 Jan 30;63(3):225-30 PMID: 2869459
  28. Quisqualate activates a rapidly inactivating high conductance ionic channel in hippocampal neurons.
    Science. 1989 Mar 17;243(4897):1474-7 PMID: 2467378
  29. Synaptic activation of N-methyl-D-aspartate receptors in the Schaffer collateral-commissural pathway of rat hippocampus.
    J Physiol. 1988 May;399:283-300 PMID: 2900332
  30. Use-dependent depression of IPSPs in rat hippocampal pyramidal cells in vitro.
    J Neurophysiol. 1985 Feb;53(2):557-71 PMID: 2984352
  31. Mixed-agonist action of excitatory amino acids on mouse spinal cord neurones under voltage clamp.
    J Physiol. 1984 Sep;354:29-53 PMID: 6148411
  32. Magnesium gates glutamate-activated channels in mouse central neurones.
    Nature. 1984 Feb 2-8;307(5950):462-5 PMID: 6320006
  33. Concanavalin A selectively reduces desensitization of mammalian neuronal quisqualate receptors.
    Proc Natl Acad Sci U S A. 1989 Feb;86(4):1411-5 PMID: 2537497
  34. Voltage-clamp analysis of mossy fiber synaptic input to hippocampal neurons.
    J Neurophysiol. 1983 Aug;50(2):487-507 PMID: 6136553
  35. Rapid desensitization of glutamate receptors in vertebrate central neurons.
    Proc Natl Acad Sci U S A. 1988 Jun;85(12):4562-6 PMID: 2898144
  36. Glutamate activates multiple single channel conductances in hippocampal neurons.
    Nature. 1987 Feb 5-11;325(6104):522-5 PMID: 2433593
  37. Phorbol diesters stimulate somatostatin secretion from cultured brain cells.
    Endocrinology. 1983 Jul;113(1):200-8 PMID: 6407821
  38. Quisqualate- and kainate-activated channels in mouse central neurones in culture.
    J Physiol. 1988 May;399:227-45 PMID: 2457088
  39. Glutamate receptor desensitization and its role in synaptic transmission.
    Neuron. 1989 Aug;3(2):209-18 PMID: 2576213
  40. Dual-component amino-acid-mediated synaptic potentials: excitatory drive for swimming in Xenopus embryos.
    J Physiol. 1985 Jun;363:35-59 PMID: 2862278
  41. Frequency-dependent N-methyl-D-aspartate receptor-mediated synaptic transmission in rat hippocampus.
    J Physiol. 1988 May;399:301-12 PMID: 2900333
  42. A persistent postsynaptic modification mediates long-term potentiation in the hippocampus.
    Neuron. 1988 Dec;1(10):911-7 PMID: 2908443
  43. Effects of new non-N-methyl-D-aspartate antagonists on synaptic transmission in the in vitro rat hippocampus.
    J Physiol. 1989 Jul;414:317-36 PMID: 2575162
  44. Dynamic changes of excitatory amino acid receptors in the rat hippocampus following transient cerebral ischemia.
    J Neurosci. 1989 Mar;9(3):798-805 PMID: 2538582
  45. A quantitative description of end-plate currents.
    J Physiol. 1972 May;223(1):173-97 PMID: 5046143
  46. Phorbol esters enhance transmitter release in rat hippocampal slices.
    Brain Res. 1987 Feb 10;403(1):198-203 PMID: 2881605
  47. The action of N-methyl-D-aspartic acid on mouse spinal neurones in culture.
    J Physiol. 1985 Apr;361:65-90 PMID: 2580984
  48. Short-term synaptic plasticity.
    Annu Rev Neurosci. 1989;12:13-31 PMID: 2648947
  49. Quinoxalinediones: potent competitive non-NMDA glutamate receptor antagonists.
    Science. 1988 Aug 5;241(4866):701-3 PMID: 2899909
  50. Dendritic spines: role of active membrane in modulating synaptic efficacy.
    Brain Res. 1985 Jan 28;325(1-2):331-5 PMID: 2579708
  51. Phorbol ester, an activator of protein kinase C, enhances calcium-dependent release of sympathetic neurotransmitter.
    Naunyn Schmiedebergs Arch Pharmacol. 1985 Oct;331(1):122-4 PMID: 2866448
  52. The role of divalent cations in the N-methyl-D-aspartate responses of mouse central neurones in culture.
    J Physiol. 1988 May;399:247-66 PMID: 2457089
  53. Facilitation of hippocampal long-lasting potentiation by GABA antagonists.
    Acta Physiol Scand. 1985 Sep;125(1):159-72 PMID: 2996303
Article Info
Journal
The Journal of physiology
Abbr.
J Physiol
ISSN
0022-3751
DOI
10.1113/jphysiol.1990.sp017980
Published
1990-03-00
Pages
203-25
Language
English
Region
England
NLM ID
0266262
PMCID
PMC1190128
Subset
IM
Grants
NIMH NIH HHS · MH-0037 · United States
NIMH NIH HHS · MH-38256 · United States
NINDS NIH HHS · NS-24205 · United States
External Links
PubMed source DOI: 10.1113/jphysiol.1990.sp017980 PMC Full Text View journal details
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