Role of the group III metabotropic glutamate receptor in LTP, depotentiation and LTD in the dentate gyrus of freely moving rats

Abstract

We investigated whether group III metabotropic glutamate (mGlu) receptors are critically involved in the expression of long-term potentiation (LTP), depotentiation, or long-term depression (LTD) in the dentate gyrus of freely moving rats. Male Wistar rats (7–8 weeks) underwent implantation of stimulating and recording electrodes in the medial perforant path and dentate gyrus granule cell layer, respectively. A cannula was permanently implanted into the ipsilateral cerebral ventricle to enable drug administration. Intracerebral injection of the group III mGlu receptor agonist, L(+)-2-amino-4-phosphonobutanoic acid (AP4), significantly inhibited LTP at a concentration which unaffects basal synaptic transmission. Depotentiation, short-term depression (STD) and LTD were unaffected by the agonist. The antagonist, (R,S)-α-cyclopropyl-4-phosphonophenylglycine (CPPG), inhibited agonist effects, but had no independent effects on basal synaptic transmission. CPPG did not affect the profile of LTP, depotentiation or STD elicited by low frequency stimulation (LFS) at 0.5 or 3 Hz, but significantly impaired LTD expression (at 1 Hz) and STD elicited at 5 Hz. These findings suggest that activation of group III mGlu receptors is critically required for LTD, but not LTP or depotentiation in the dentate gyrus and provide evidence for the involvement of separate mechanisms underlying LTD and depotentiation.