Frequency-dependent noradrenergic modulation of long-term potentiation in the hippocampus.

Norepinephrine, briefly superfused during high-frequency stimulation of the mossy fibers in the rat hippocampal slice in vitro, produced a reversible increase in the magnitude, duration, and probability of induction of long-term synaptic potentiation in the CA3 subfield. Similar results were obtained with isoproterenol, whereas propranolol or timolol reversibly blocked long-term potentiation. Norepinephrine had little apparent effect on responses obtained during low-frequency stimulation of the mossy fibers. These data suggest that norepinephrine can mediate long-lasting, frequency-dependent modulation of synaptic transmission in the mammalian brain. Furthermore, the results suggest a plausible mechanism for some of the known associative interactions between synaptic inputs to hippocampal neurons.