Neural mechanisms for spatial memory formation are believed to comprise an integration of processes mediated by hippocampal synaptic plasticity in the form of long-term potentiation (LTP) and long-term depression (LTD). Novel space consists of several types of information, but that may evoke differential responses in individual hippocampal subregions. In CA1, CA3 and dentate gyrus (DG) subregions and at multiple types of hippocampal synapses (perforant path-DG, mossy fi ber-CA3, Schaffer collateral-CA1) exploration of a novel empty environment facilitates the expression of robust LTP (>24 h) in freely behaving animals. In contrast, LTD facilitation is subregionand synapse- specifi c and dependent on the nature of the cues. In the CA1 region, partially concealed, small, contextual cues facilitate LTD. LTD in DG is facilitated by large directional cues. Arousal, mediated by activation of the noradrenergic (NA) system is a critical factor in information acquisition and may enhance the encoding of novel spatial information. We observed that learning-facilitated induction of LTD is inhibited by β-adrenoreceptor antagonist, and facilitation of LTD and the encoding of spatial memory is elicited when the locus coeruleus is activated. These results suggest that β-adrenoreceptors may facilitate encoding of spatial information through synaptic plasticity in the hippocampus and that NA released by the locus coeruleus during novel exploration, is a key factor in effective information acquisition.