Dependence of long-term depression on postsynaptic metabotropic glutamate receptors in visual cortex.

Long-term depression (LTD) is held relevant to memory and learning. Its induction is known to require postsynaptic calcium increases. However, the source of these calcium increases remains unclear. In visual cortex slices, LTD was induced by tetanization after blockade of N-methyl-D-aspartate (NMDA) and non-NMDA ionotropic glutamate receptors. LTD induced under this condition was prevented by an intracellular injection of each of the following drugs into the postsynaptic neuron: (i) guanosine 5'-[beta-thio]diphosphate, which competitively inhibits the binding of GTP to GTP-binding regulatory proteins; (ii) heparin, which antagonizes 1,4,5-inositol triphosphate binding; and (iii) calcium chelators. Moreover, LTD was induced without tetanization by applying quisqualate (10 microM), a metabotropic glutamate receptor agonist, but not another agonist, trans-aminocyclopentane-1,3-dicarboxylic acid (10 microM). Together, these results suggest that activation of 1,4,5-inositol trisphosphate-linked subtypes of metabotropic glutamate receptor is responsible for the increase in postsynaptic calcium concentration, which results in homosynaptic LTD.