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Key Words excitatory, transmission, memory, LTP, LTD
Abstract Activity-dependent changes in synaptic function are believed to underlie the formation of memories. Two prominent examples are long-term potentiation (LTP) and long-term depression (LTD), whose mechanisms have been the subject of considerable scrutiny over the past few decades. Here we review the growing literature that supports a critical role for AMPA receptor trafficking in LTP and LTD, focusing on the roles proposed for specific AMPA receptor subunits and their interacting proteins. While much work remains to understand the molecular basis for synaptic plasticity, recent results on AMPA receptor trafficking provide a clear conceptual framework for future studies.
INTRODUCTION
It is widely believed that a long-lasting change in synaptic function is the cellular basis of learning and memory (Alkon & Nelson 1990, Eccles 1964, Hebb 1949, Kandel 1997). The most thoroughly characterized examples of such synaptic plasticity in the mammalian nervous system are long-term potentiation (LTP) and long-term depression (LTD). A remarkable feature of LTP and LTD is that a short period of synaptic activity (either high- or low-frequency stimulation) can trigger persistent changes of synaptic transmission lasting at least several hours and often longer. This single property initially led investigators to suggest that these forms of plasticity are the cellular correlate of learning (Bliss & Gardner-Medwin 1973, Bliss & Lomo 1973). Work over the past 25 years that has elucidated many properties of LTP and LTD reinforces this view as well as suggests their involvement in various other physiological as well as pathological processes (Martin et al. 2000, Zoghbi et al. 2000).
Much effort in the field has been directed toward understanding the detailed molecular mechanisms that account for the change in synaptic efficacy. For many years, a most basic question remained intractable: Is the change in synaptic strength during these forms of plasticity primarily due to a pre- or postsynaptic modification? Numerous experiments using a variety of approaches were directed toward answering this question. Surprisingly, they often yielded conflicting conclusions (Kullmann & Siegelbaum 1995). Although many studies suggested primarily postsynaptic modifications (Davies et al. 1989, Kauer et al. 1988, Manabe et al. 1992, Muller et al. 1988), a consistent finding was a change in synaptic failures after LTP (Isaac et al. 1996, Kullmann &...