Nomadic AMPA Receptors and LTP

leased glutamate could explain the electrophysiological changes observed during LTP that have been attributed to an increase in presynaptically released neurotrans-Long-term potentiation (LTP) is one of the most widely mitters. In support of the silent synapse hypothesis, studied topics in neuroscience today. LTP refers to a electrophysiological and immunohistochemical studies long-lasting increase of synaptic efficacy that depends have revealed a substantial number of synapses that on appropriate synapse use. Because it is rapidly ex-contain only NMDA receptors and are devoid of func-pressed in the right place, the hippocampus, in the man-tional AMPA receptors (9%–14% in adult rat hippocam-ner expected of a cellular substrate for particular types pus: Malinow, 1998, and references therein). of memory, LTP has intrigued many neurobiologists. Its Additional evidence for the silent synapse hypothesis popularity is evident in the fact that LTP has been tack-for LTP comes from studies of brain development. LTP led by a remarkably divergent set of approaches, from has been proposed to be important for maturation of molecular and cellular studies to those involving animal neural circuits by providing a mechanism for strengthen-behavior. Two recent reports on LTP mechanisms are a ing appropriate connections. Accordingly, conversion striking reminder of the surprises that scientific research of silent synapses into AMPA-responsive synapses has can deliver (Shi et al., 1999; Zamanillo et al., 1999). The been demonstrated in various regions of the developing new findings reveal an exciting cell biological correlate brain (Malenka and Nicoll, 1997). Although LTP has not of LTP while cautioning us that the LTP/memory connec-been confirmed as a requirement for remodeling of neu-tion may be less direct than many have believed. ral circuits, the coincident loss of silent synapses and A Bit of History susceptibility to LTP favors the conversion of silent syn-To appreciate the importance of the new findings, a brief apses as a possible mechanism for LTP expression. account of LTP and glutamate receptors is in order. Functional AMPA receptors might be recruited to Excitatory synaptic transmission at central synapses is awaken silent synapses in at least three different ways. largely mediated by the AMPA-class of glutamate recep-First, they could be synthesized de novo, either in the tors. Nevertheless, the subclass of glutamate receptors soma and rapidly delivered to the dendritic spines or translated directly in the dendrites. Second, the recep-that have received most attention in LTP is the N-methyl-tors already present in the postsynaptic density in an D-aspartate (NMDA) …