Associative long-term depression in the hippocampus is dependent on postsynaptic N-type Ca(2+) channels Journal Article

Author(s): Normann, Claus; Peckys, Diana; Schulze, Christian H; Walden, Jörg; Jonas, Peter; Bischofberger, Joseph
Article Title: Associative long-term depression in the hippocampus is dependent on postsynaptic N-type Ca(2+) channels
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 of D-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-HT(1A) 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.
Keywords: Hippocampus; Associative long-term depression; Asynchronous pairing; Metabotropic glutamate receptors; N-type Ca2+ channels; NMDA receptors
Journal Title: Journal of Neuroscience
Volume: 20
Issue 22
ISSN: 1529-2401
Publisher: Society for Neuroscience  
Date Published: 2000-11-15
Start Page: 8290
End Page: 8297
Copyright Statement: Copyright © 2000 Society for Neuroscience
Open access: no