This chapter compares the cellular mechanisms that have been implicated in the induction and expression of long-term depression (LTD) at Schaffer collateral-CA1 synapses to perforant path-dentate gyrus (DG) synapses. In general, Schaffer collateral LTD and long-term potentiation (LTP) both appear to be a complex combination of many alterations in synaptic transmission that occur at both presynaptic and postsynaptic sites, while at perforant path synapses, most evidence has focused on postsynaptic long-term alterations. Within the DG, the medial perforant path is far more studied than lateral perforant path synapses, where most evidence relates to the induction of heterosynaptic LTD at lateral perforant path synapses when LTP is induced in the medial perforant path. Of course, there remain many other classes of synapses in the DG where synaptic plasticity, including LTD, have been largely neglected. It is clear that a better understanding of the range of DG loci where long-lasting activity-dependent plasticity, both LTD and LTP, are expressed will be essential to improve our understanding of the cognitive roles of such DG plasticity.