History and Definition In 1973, two reports appeared in the Journal of Physiology that described a long-term potentiation (L TP) of synaptic transmission at a monosynaptic junction in the mammalian eNS. These two papers, one dealing with the anesthetized rabbit preparation (Bliss & L0mo 1973) and the other dealing with the unanesthetized rabbit (Bliss & Gardner-Medwin 1973), were of considerable interest because they marked the first demonstration of a neurophysiological alteration in the mammalian brain possessing a con­ siderable time-course. Prior to these observations, neurophysiological phenomena were known to be of relatively modest temporal extent. The experiments of Bliss and colleagues showed that in the perforant path to dentate gyrus synapse, substantial increases in synaptic efficacy were observed following tetanic stimulation of afferent fibers. Synaptic efficacy refers to the postsynapti c response to a constant afferent volley. The changes (on the order of a 50% increase in the amplitude of the response) lasted for at least ten hours in the anesthetized preparation and up to 16 weeks in the unanesthetized preparation following a series of tetanic stimuli . These results attracted great interest because of the possi­ bility that the phenomenon might underlie some aspects of memory storage. A critical question-not yet completely answered-was stated by Bliss & Lemo : "Whether or not the intact animal makes use in real life of a property which has been revealed by synchronous, repetitive volleys to a population of fibers the normal and pattern of activity along which are unknown, is another matter" (Bliss & L0mo 1973, p. 355). As we shall see, the available evidence suggests that L TP does occur in conjunction with behavioral learning-although whether it is necessary and sufficient is far from certain.