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ARTICLE, Cellular/Molecular

Associative Long-Term Depression in the Hippocampus Is Dependent on Postsynaptic N-Type Ca2+ Channels

Claus Normann, Diana Peckys, Christian H. Schulze, Jörg Walden, Peter Jonas and Josef Bischofberger
Journal of Neuroscience 15 November 2000, 20 (22) 8290-8297; DOI: https://doi.org/10.1523/JNEUROSCI.20-22-08290.2000
Claus Normann
1Institute of Physiology, University of Freiburg, D-79104 Freiburg, Germany, and
2Department of Psychiatry, University of Freiburg, D-79104 Freiburg, Germany
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Diana Peckys
1Institute of Physiology, University of Freiburg, D-79104 Freiburg, Germany, and
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Christian H. Schulze
1Institute of Physiology, University of Freiburg, D-79104 Freiburg, Germany, and
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Jörg Walden
2Department of Psychiatry, University of Freiburg, D-79104 Freiburg, Germany
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Peter Jonas
1Institute of Physiology, University of Freiburg, D-79104 Freiburg, Germany, and
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Josef Bischofberger
1Institute of Physiology, University of Freiburg, D-79104 Freiburg, Germany, and
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Abstract

Long-term depression (LTD) is a form of synaptic plasticity that can be induced either by low-frequency stimulation of presynaptic fibers or in an associative manner by asynchronous pairing of presynaptic and postsynaptic activity. We investigated the induction mechanisms of associative LTD in CA1 pyramidal neurons of the hippocampus using whole-cell patch-clamp recordings and Ca2+ imaging in acute brain slices. Asynchronous pairing of postsynaptic action potentials with EPSPs evoked with a delay of 20 msec induced a robust, long-lasting depression of the EPSP amplitude to 43%. Unlike LTD induced by low-frequency stimulation, associative LTD was resistant to the application ofd-AP-5, indicating that it is independent of NMDA receptors. In contrast, associative LTD was inhibited by (S)-α-methyl-4-carboxyphenyl-glycine, indicating the involvement of metabotropic glutamate receptors. Furthermore, associative LTD is dependent on the activation of voltage-gated Ca2+ channels by postsynaptic action potentials. Both nifedipine, an L-type Ca2+ channel antagonist, and ω-conotoxin GVIA, a selective N-type channel blocker, abolished the induction of associative LTD. 8-hydroxy-2-dipropylaminotetralin (OH-DPAT), a 5-HT1Areceptor agonist, inhibited postsynaptic Ca2+ influx through N-type Ca2+ channels, without affecting presynaptic transmitter release. OH-DPAT also inhibited the induction of associative LTD, suggesting that the involvement of N-type channels makes synaptic plasticity accessible to modulation by neurotransmitters. Thus, the modulation of N-type Ca2+ channels provides a gain control for synaptic depression in hippocampal pyramidal neurons.

  • associative long-term depression
  • hippocampus
  • N-type Ca2+ channels
  • NMDA receptors
  • metabotropic glutamate receptors
  • asynchronous pairing
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The Journal of Neuroscience: 20 (22)
Journal of Neuroscience
Vol. 20, Issue 22
15 Nov 2000
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Associative Long-Term Depression in the Hippocampus Is Dependent on Postsynaptic N-Type Ca2+ Channels
Claus Normann, Diana Peckys, Christian H. Schulze, Jörg Walden, Peter Jonas, Josef Bischofberger
Journal of Neuroscience 15 November 2000, 20 (22) 8290-8297; DOI: 10.1523/JNEUROSCI.20-22-08290.2000

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Associative Long-Term Depression in the Hippocampus Is Dependent on Postsynaptic N-Type Ca2+ Channels
Claus Normann, Diana Peckys, Christian H. Schulze, Jörg Walden, Peter Jonas, Josef Bischofberger
Journal of Neuroscience 15 November 2000, 20 (22) 8290-8297; DOI: 10.1523/JNEUROSCI.20-22-08290.2000
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Keywords

  • associative long-term depression
  • hippocampus
  • N-type Ca2+ channels
  • NMDA receptors
  • metabotropic glutamate receptors
  • asynchronous pairing

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