Time-dependent induction of depotentiation in the dentate gyrus of freely moving rats: involvement of group 2 metabotropic glutamate receptors

Depotentiation comprises a reversal of tetanization-induced long-term poten tiation (LTP) which occurs following low-frequency stimulation (LFS) in the hippocampus in vivo. Although depotentiation has been consistently demonst rated in the CA1 region, no positive reports of the existence of depotentia tion in the dentate gyrus in vivo have occurred. This study therefore inves tigated whether depotentiation is possible in the dentate gyrus in vivo. We found that depotentiation can be induced, but it is very tightly dependent on the interval between tetanization and LFS, Thus, LFS given 2 or 5 min f ollowing tetanization produced significant depotentiation, whereas LFS give n 10-30 min following tetanization had no significant effect on the express ion of LTP. Depotentiation occurred in two phases: a transient depression o f evoked responses to below pre-tetanization values, which occurred in the first 60 min following LFS, and a recovery of this response to a stable lev el of synaptic transmission which comprised a significant reduction in the magnitude of LTP. Group 2 metabotropic glutamate receptors (mGluRs) play an important role in the expression of long-term depression in vivo. We there fore investigated whether group 2 mGluRs contribute to depotentiation. The group 2 antagonist (2S)-alpha-ethylglutamic acid (EGLU) inhibited the early transient depression at a concentration which inhibits LTD in vivo, but di d not block the expression of depotentiation. EGLU also inhibited the trans ient depression induced by 5 Hz given alone. Increasing the concentration o f EGLU prevented depotentiation, however. The group 2 agonist (S)-4-carboxy -3-hydroxyphenylglycine (4C3HPG) inhibited LTP and enhanced depotentiation. These data suggest a role for group 2 mGluRs in depotentiation.