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The Journal of Neuroscience, June 1, 2001, 21(11):3705-3714
Time-Dependent Reversal of Long-Term Potentiation by
Low-Frequency Stimulation at the Hippocampal Mossy
Fiber-CA3 Synapses
Yea-Lin
Chen,
Chiung-Chun
Huang, and
Kuei-Sen
Hsu
Department of Pharmacology, College of Medicine, National
Cheng-Kung University, Tainan City 701, Taiwan
Using mouse hippocampal slices, we studied the induction of
depotentiation of long-term potentiation (LTP) at the mossy fiber synapses onto CA3 pyramidal neurons. A long train of low-frequency (1 Hz/900 pulses) stimulation (LFS) induced a long-term depression of
baseline synaptic transmission or depotentiation of previously established LTP, which was reversible and was independent of
NMDA receptor activation. This LFS-induced depotentiation was observed when the stimulus was delivered 1 or 10 min after LTP induction. However, when LFS was applied at 30 min after induction, significantly less depotentiation was found. The induction of depotentiation on one
input was associated with a heterosynaptic reverse of the LTP induced
previously on a separate pathway. In addition, this LFS-induced
depotentiation appeared to be mediated by the activation of group 2 metabotropic glutamate receptors (mGluRs), because it was mimicked by
the bath-applied group 2 agonist
(2S,2'R,3'R)-2-(2', 3'-dicarboxycyclopropyl) glycine and was specifically inhibited by the group 2 antagonists
(S)- -methyl-4-carboxyphenylglycine and
(S)--amino--(1S,2S)-2-carboxycyclopropyl-9H-xanthine-9-propanic acid. Moreover, the induction of depotentiation was entirely normal when synaptic transmission is blocked by glutamate receptor antagonist kynurenic acid and was associated with a reversal of paired-pulse facilitation attenuation during LTP expression. Pretreatment of the
hippocampal slices with Gi/o-protein inhibitor pertussis
toxin (PTX) prevented the LFS-induced depotentiation. These results suggest that the activation of presynaptic group 2 mGluRs and in turn
triggering a PTX-sensitive Gi/o-protein-coupled signaling cascade may contribute to the LFS-induced depotentiation at the mossy
fiber-CA3 synapses.
Key words:
long-term potentiation (LTP); long-term depression (LTD); depotentiation; metabotropic glutamate receptor (mGluR); mossy fiber
pathway; hippocampus
Copyright © 2001 Society for Neuroscience 0270-6474/01/21113705-10$05.00/0
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