The perforant path-dentate gyrus synapse has provided a model system for functional neural plasticity in adult mammalian brain. NMDA-dependent long-term changes in neural connectivity occur at this synapse in response to high-frequency input. Norepinephrine (NE) applied exogenously or released endogenously can initiate both a short- and a long-term potentiation (LTP) of the dentate gyrus response to perforant path input. Triggering of the potentiated response depends on beta-receptor activation and does not require a high-frequency stimulus. An increase in locus coeruleus (LC) activity can initiate both short and LTP of the perforant path response, although a reduction in LC activity does not alter baseline perforant path responses. This chapter considers differences between NE modulation in vitro and in vivo, differences and similarities between NE-LTP and frequency-induced LTP, and the surprising specificity of NE effects at the perforant path synapse. Studies of NE in the dentate gyrus support a role for the LC in promoting both short- and long-term enhancement of responses to complex sensory inputs and are consistent with a role for the LC in memorial as well as attentional processes.