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Volume 17, Number 9,
Issue of May 1, 1997
pp. 3303-3311
Copyright ©1997 Society for Neuroscience
Group 1 and 2 Metabotropic Glutamate Receptors Play Differential
Roles in Hippocampal Long-Term Depression and Long-Term Potentiation in
Freely Moving Rats
Received Dec. 20, 1996; revised Feb. 7, 1997; accepted Feb. 13, 1997.
Denise Manahan-Vaughan
Federal Institute for Neurobiology, Department of Neurophysiology,
D-39008 Magdeburg, Germany
This study examined the role of metabotropic glutamate
receptors (mGluRs) in hippocampal long-term depression (LTD) in
vivo. The group 1 mGluR antagonist
(S)4-carboxyphenylglycine (4CPG), group 1/2 antagonist
(RS)- -methyl-4-carboxyphenylglycine (MCPG), and group
2 antagonists
(RS)--methylserine-O-phos-phate
monophenyl ester (MSOPPE) and (2S)--ethylglutamic
acid (EGLU) were used. The NMDA receptor antagonist
D( )-2-amino-5-phosphonopentanoic acid (AP5) was used to
examine the NMDA receptor contribution to the observed LTD. Adult male
Wistar rats underwent implantation of stimulating and recording
electrodes into the Schaffer collaterals and CA1 stratum radiatum,
respectively. After recovery of 5-7 d, the field EPSP was measured
from freely moving animals. Drugs were applied either before or after 1 Hz low-frequency train (LFT) or 100 Hz stimulation via a cannula
implanted in the lateral cerebral ventricle. Nine hundred pulses at 1 Hz produced an LTD that was marked and long-lasting. This LTD was
completely inhibited by pre-LFT application of AP5. MCPG inhibited LTD
from 2 hr post-LFT. 4CPG partially impaired LTD. MSOPPE and EGLU
completely blocked induction of LTD, although short-term depression
remained intact. MSOPPE did not block long-term potentiation (LTP)
induced by 100 Hz stimulation, whereas 4CPG produced a significant
inhibition. When MSOPPE was present, LTD could not be induced either
before or after LTP induction, whereas LTD could be induced in an
identical protocol in vehicle-injected animals.
These results suggest a differential role for mGluRs in NMDA
receptor-dependent hippocampal LTD in vivo. Group 1 mGluRs may play a role in both LTD and LTP, whereas group 2 mGluRs may
be critically involved only in LTD induction.
Key words:
metabotropic glutamate receptors;
long-term depression;
long-term potentiation;
in vivo;
hippocampus;
NMDA
receptors
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