Two forms of hippocampal long-term depression, the counterpart of long-term potentiation

In the hippocampus there are two distinct forms of long-term depression (LTD) of excitatory synaptic transmission. In the CA1 region, prolonged low-frequency stimulation induces LTD by activating postsynaptic NMDA receptors, which causes a moderate rise in Ca2+ concentrations. In messy fiber synapses of the CA3 region, similar low-frequency stimulation also gives rise to LTD, However, this form of LTD (messy fiber LTD) does not require activation of NMDA receptors, but is mediated by activation of presynaptic metabotropic glutamate receptors, Induction of messy fiber LTD is not dependent on postsynaptic depolarization or activation of postsynaptic ionotropic glutamate receptors, thus it is likely to be mediated by purely presynaptic mechanisms, This conclusion is confirmed by the analysis of mutant mice lacking presynaptic mGluR2, in which messy fiber LTD is almost absent, Since long-term potentiation at messy fiber synapses is also induced presynaptically, the synaptic efficacy may be regulated through common mechanisms bidirectionally, which may contribute to neural information processing in the hippocampus.