Differential Regulation of Dendrite Complexity by AMPA Receptor Subunits GluR1 and GluR2 in Motor Neurons Ranjini Prithviraj, 1 Kristen M. Kelly, 1 * Ramon Espinoza-Lewis, 1{ Tia Hexom, 1 Amy B. Clark, 2{ Fiona M. Inglis 1 1 Department of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana 70118 2 Undergraduate Neuroscience Program, Tulane University, New Orleans, Louisiana 70118 Received 22 May 2007; revised 6 September 2007; accepted 3 October 2007 ABSTRACT: Activity-dependent developmental mechanisms in many regions of the central nervous sys- tem are thought to be responsible for shaping dendritic architecture and connectivity, although the molecular mechanisms underlying these events remain obscure. Since AMPA glutamate receptors are developmentally regulated in spinal motor neurons, we have investigated the role of activation of AMPA receptors in dendritic outgrowth of spinal motor neurons by overexpression of two subunits, GluR1 and GluR2, and find that dendrite outgrowth is differentially controlled by expression of these subunits. Overexpression of GluR1 was associated with greater numbers of filopodia, and an increase in the length and complexity of dendritic arbor. In con- trast, GluR2 expression did not alter dendritic complex- ity, but was associated with a moderate increase in length of arbor, and decreased numbers of filopodia. Neither GluR1 nor GluR2 had any effect on the motility of filopodia. In addition, GluR1 but not GluR2 expres- sion increased the density of dendritic puncta incorpo- rating a GFP-labeled PSD95, suggesting that GluR1 may mediate its effect in part by augmenting the num- ber of excitatory synapses within motor neuron den- drites. Together these results suggest that in spinal motor neurons, AMPA receptors composed of GluR1 subunits may facilitate neurotrophic mechanisms in these neurons, permitting sustained dendrite outgrowth and synaptogenesis, whereas expression of AMPA receptors containing GluR2 acts to preserve existing dendritic arbor. Thus, the observed downregulation of GluR1 in motor neurons during postnatal development may limit the formation of new dendrite segments and synapses, promoting stabilized synaptic connectivity. ' 2007 Wiley Periodicals, Inc. Develop Neurobiol 68: 247–264, 2008 Keywords: AMPA receptor; dendrite branching; filopodia; motor neuron; PSD95 Contract grant sponsor: National Science Foundation; contract grant number: 0446168. Contract grant sponsor: NIH/NIGMS CoBRE; contract grant number: 1 P20 RR 15637. Contract grant sponsor: the Louisiana Board of Regents; contract grant number: LEQSF (2003-2006)-RD-A-24. ' 2007 Wiley Periodicals, Inc. Published online 13 November 2007 in Wiley InterScience (www. interscience.wiley.com). DOI 10.1002/dneu.20590 This article contains supplementary material available via the Internet at http://www.mrw.interscience.wiley.com/suppmat/1932- 8451/suppmat/ *Present address: Stritch School of Medicine, Loyola University, Chicago, IL. { Present address: Oral Biology Department, College of Dentistry, Ohio State University, Columbus, OH. { Present address: Georgetown Medical School, Washington, DC. Correspondence to: F.M. Inglis (inglis@tulane.edu). 247