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The Journal of Neuroscience, November 15, 2000, 20(22):8290-8297
Associative Long-Term Depression in the Hippocampus Is Dependent
on Postsynaptic N-Type Ca2+ Channels
Claus
Normann1, 2,
Diana
Peckys1,
Christian H.
Schulze1,
Jörg
Walden2,
Peter
Jonas1, and
Josef
Bischofberger1
1 Institute of Physiology, University of Freiburg,
D-79104 Freiburg, Germany, and 2 Department of Psychiatry,
University of Freiburg, D-79104 Freiburg, Germany
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 of
D-AP-5, indicating that it is independent of NMDA
receptors. In contrast, associative LTD was inhibited by
(S)- -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  -conotoxin GVIA, a selective N-type channel
blocker, abolished the induction of associative LTD.
8-hydroxy-2-dipropylaminotetralin (OH-DPAT), a 5-HT1A
receptor 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.
Key words:
associative long-term depression; hippocampus; N-type
Ca2+ channels; NMDA receptors; metabotropic
glutamate receptors; asynchronous pairing
Copyright © 2000 Society for Neuroscience 0270-6474/00/20228290-08$05.00/0
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