Spatial memory formation is enabled through synaptic information processing, in the form of persistent strengthening and weakening of synapses, within the hippocampus. It is, however, unclear how relevant spatial information is selected for encoding, in preference to less pertinent information. As the noradrenergic locus coeruleus (LC) becomes active in response to novel experiences, we hypothesized that the LC may provide the saliency signal required to promote hippocampal encoding of relevant information through changes in synaptic strength. Test pulse stimulation evoked stable basal synaptic transmission at Schaffer collateral (SC)-CA1 stratum radiatum synapses in freely behaving adult rats. Coupling of these test pulses with electrical stimulation of the LC induced long-term depression (LTD) at SC-CA1 synapses and induced a transient suppression of theta-frequency oscillations. Effects were N-methyl-D-aspartate and beta-adrenergic receptor dependent. Activation of the LC also increased CA1 noradrenalin levels and facilitated the encoding of spatial memory for a single episode via a beta-adrenoceptor-dependent mechanism. Our results demonstrate that the LC plays a key role in the induction of hippocampal LTD and in promoting the encoding of spatial information. This LC-hippocampal interaction may reflect a means by which salient information is distinguished for subsequent synaptic processing.