Nature Neuroscience7, 244 - 253 (2004)
Published online: 8 February 2004; | doi:10.1038/nn1189
Activity-dependent regulation of dendritic synthesis and trafficking of AMPA receptors
William Ju1, Wade Morishita1, Jennifer Tsui1, Guido Gaietta2, Thomas J Deerinck2, Stephen R Adams3, Craig C Garner1, Roger Y Tsien3, Mark H Ellisman2
& Robert C Malenka1
1
Nancy Friend Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, 1201 Welch Road, Stanford University School of Medicine, Palo Alto, California 94304, USA.
2
National Center for Microscopy & Imaging Research, Department of Neurosciences 0608, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
3
Department of Pharmacology, Howard Hughes Medical Institute, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
Regulation of AMPA receptor (AMPAR) trafficking is important for neural plasticity. Here we examined the trafficking and synthesis of the GluR1 and GluR2 subunits using ReAsH-EDT2 and FlAsH-EDT2 staining. Activity blockade of rat cultured neurons increased dendritic GluR1, but not GluR2, levels. Examination of transected dendrites revealed that both AMPAR subunits were synthesized in dendrites and that activity blockade enhanced dendritic synthesis of GluR1 but not GluR2. In contrast, acute pharmacological manipulations increased dendritic synthesis of both subunits. AMPARs synthesized in dendrites were inserted into synaptic plasma membranes and, after activity blockade, the electrophysiological properties of native synaptic AMPARs changed in the manner predicted by the imaging experiments. In addition to providing a novel mechanism for synaptic modifications, these results point out the advantages of using FlAsH-EDT2 and ReAsH-EDT2 for studying the trafficking of newly synthesized proteins in local cellular compartments such as dendrites.
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