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Closed Access item Cellular Biology of AMPA Receptor Trafficking and Synaptic Plasticity

Authors:Esteban, J. A.
Keywords:AMPA, Glutamate receptors
Issue Date:2008
Publisher:Springer
Citation:Structural And Functional Organization Of The Synapse, 271-287 (2008)
Abstract:Intracellular membrane trafficking is an essential process in all eukaryotic cells, but it is particularly critical at synaptic terminals, where a large number of specific ion channels, scaffolding molecules and multiple signal transduction regulators have to be precisely targeted to ensure proper synaptic function (80, 126). At the level of the postsynaptic terminal, local membrane trafficking is now appreciated as major factor controlling synaptic function (58). In particular, the regulation of neurotransmitter receptor transport and targeting is crucial for the maintenance of synaptic strength, and for the activity-dependent changes associated to synaptic plasticity (19). Most excitatory transmission in the central nervous system is mediated by two types of glutamate receptors: γ-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors. These two types of receptors have very different roles in synaptic function (22, 51). AMPA receptors (AMPARs) mediate most excitatory (depolarizing) currents in conditions of basal neuronal activity. Hence, they have a major influence in the strength of the synaptic response. NMDA receptors (NMDARs), on the other hand, remain silent at resting membrane potential (85), but they are crucial for the induction of specific forms of synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD) (6). Although AMPARs and NMDARs reside at the same synapses in most brain regions, they traffic to the synaptic membrane through quite different programs. In the brain, soon after birth, most excitatory synapses in the hippocampus and other brain regions contain only NMDARs, whereas the prevalence of AMPARs increases gradually over development (24, 53, 55, 73, 92). In fact, the delivery of AMPARs into synapses is a regulated process that depends on NMDAR activation and underlies some forms of synaptic plasticity (78). Synaptic plasticity is thought to underlie higher cognitive functions, such as learning and memory (9, 90, 119), and is also critical for neural development (20). Thus, it is not surprising that alterations in synaptic plasticity have been implicated in the pathology of several neurological disorders, including Alzheimer’s disease (98), schizophrenia (110), Down’s syndrome (32) and other forms of mental retardation (82). Consequently, there is considerable interest in understanding the underlying mechanisms of synaptic plasticity, among which the regulation of AMPAR trafficking plays a prominent role. This review will summarize our current knowledge of the membrane trafficking pathways that steer AMPARs from their biosynthesis at the endoplasmic reticulum (ER) to their destination at excitatory synapses, with special emphasis in the regulatory steps that contribute to synaptic plasticity. Most of the experimental observations that are the basis for this chapter have been obtained from hippocampal principal neurons, although it is expected that most of the principles described here will be applicable to the regulation of AMPAR trafficking in multiple brain regions.
Publisher version (URL):http://dx.doi.org/10.1007/978-0-387-77232-5_10
URI:http://hdl.handle.net/10261/40129
ISBN:978-0-387-77231-8
Appears in Collections:(CBM) Libros y Partes de Libros

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