- Ph.D., University of Washington, 1983
- National Institutes of Health
Components of the cell are positioned and compartmentalized with exquisite precision, but the functional significance of this organization has only recently been recognized. Spatial complexity is especially prominent within the nervous system. My research addresses the organization of excitatory synapses in rodent neocortex and hippocampus. Techniques routinely used in my lab include high-resolution and quantitative light- and electron microscopic immunocytochemistry.
We performed a number of studies using light microscopic immunocytochemistry and immunogold EM to examine the relationship of AMPA and NMDA glutamate receptors to the synaptic active zone. We continue this basic line of research: Proteomics studies have identified over 100 proteins associated with the postsynaptic density (PSD). We are using quantitative immunogold methods and high-resolution electron tomography to examine the organization of a variety of these proteins, to elucidate the supramolecular architecture of the PSD. We want to use this information to explore how the organization of molecules within the synapse may help to regulate postsynaptic signaling pathways. For example, calcium ions entering through NMDA receptor channels may modify synaptic activity. Might the targets of this calcium entry (e.g., CaMKII, nNOS, or calcium-dependent adenylyl cyclase) be situated close to the NMDA pore, suitably positioned to respond selectively to calcium entry through that pore? Likewise, might specific enzymes (e.g., PKA) that can modulate AMPA receptors be held close to these receptors?
This leads to a second theme in my research, to study the anatomical basis of synaptic plasticity. Of particular interest to us is the nitric oxide/sGC signaling pathway (implicated in modulation of presynaptic release) and trafficking of AMPA receptors (implicated in the control of postsynaptic efficacy). The issue of trafficking has led us to study motor and endocytic proteins, in relation to the actin cytoskeleton.
A final theme of my current research is to explore calcium sinks and sources within dendritic spines. My lab is part of a multi-center program project grant (with Mary Kennedy, Karel Svoboda, and Terry Sejnowski), using a multidisciplinary approach to elucidate the functional significance of spines. So far, my group has focused on the organization of plasma membrane calcium pumps (PMCAs), which appear to play a considerably more complex role in calcium signaling than was previously recognized.
Left - Postembedding immunogold labelling of cofilin in stratum radiatum of the CA1 region of the hippocampus. Gold particles lie over the PSD and in the spine cytoplasm, close to the plasma membrane. Scale bar 200nm.
Right - Triple labeling of sGCα with two glial markers, S100β and GFAP in cerebellum. Some immunopositive structures in the Purkinje cell layer are also stained for S100β and GFAP; triple-labeled profiles in the molecular layer (arrowheads) are likely to be processes of Bergmann glia. Scale bar 25μm.
- Racz B, Blanpied TA, Ehlers MD, Weinberg RJ. (2004) Lateral organization of endocytic machinery in dendritic spines. Nat. Neurosci. Sept. 7;(9):917-8.
- Jen D, Parente P, Robbins J, Weigle C, Taylor R, Burette A, Weinberg R. (2004) ImageSurfer: A Tool for Visualizing Correlations between Two Volume Scalar Fields. Proceedings of the IEEE conference on Visualization. Oct.:529-536.
- Racz B, Weinberg RJ. (2004) The subcellular organization of cortactin in hippocampus. J Neurosci. Nov 17;24(46):10310-7.
- Choi J, Ko J, Racz B, Burette A, Lee JR, Kim S, Na M, Lee HW, Kim K, Weinberg RJ, Kim E. (2005) Regulation of dendritic spine morphogenesis by insulin receptor substrate 53, a downstream effector of Rac1 and Cdc42 small GTPases. J. Neurosci. Jan. 26;25(4):869-79.
- Tolias KF, Bikoff JB, Burette A, Paradis S, Harrar D, Tavazoie S, Weinberg RJ, Greenberg ME. (2005) The Rac1-GEF Tiam1 Couples the NMDA Receptor to the Activity-Dependent Development of Dendritic Arbors and Spines. Neuron. Feb. 17;45:525-538.
- Ding JD, Burette A, Weinberg RJ. (2005) Expression of soluble guanylyl cyclase in rat cerebral cortex during postnatal development. J Comp Neurol, 485(3):255-265.
- Kip SN, Gray NW, Burette A, Canbay A, Weinberg RJ, Strehler EE. (2005) Changes in the expression of plasma membrane calcium extrusion systems during the maturation of hippocampal neurons. Hippocampus. Sep. 30.
- Melone M, Burette A, Weinberg RJ. (2005) Light microscopic identification and immunocytochemical characterization of glutamatergic synapses in brain sections. J Comp Neurol, 492 (4):495-509.
- Horton AC, Racz B, Monson EE, Lin AL, Weinberg RJ, Ehlers MD. (2005) Polarized secretory trafficking directs cargo for asymmetric dendrite growth and morphogenesis. Neuron. Dec. 8;48(5):757-71.
- Racz B, Weinberg RJ. (2006) Spatial organization of cofilin in dendritic spines. Neuroscience. 138(2):447-56.
- Ryu J, Liu L, Wong TP, Wu DC, Burette A, Weinberg R, Wang YT, Sheng M. (2006) A Critical Role for Myosin IIB in Dendritic Spine Morphology and Synaptic Function. Neuron, 49(2):175-182.
- Ding JD, Weinberg RJ. (2006) Localization of soluble guanylyl cyclase in the superficial dorsal horn. J Comp Neurol. 495(6):668-678.
- Kim S, Burette A, Chung HS, Kwon SK, Woo J, Lee HW, Kim K, Kim H, Weinberg RJ, Kim E (2006) NGL family PSD-95â€“interacting adhesion molecules regulate excitatory synapse formation, Nature Neuroscience, Oct;9(10):1294-301.
- Welch JM, Lu J, Rodriguiz RM, Trotta NC, Peca J, Ding JD, Feliciano C, Chen M, Adams JP, Luo J, Dudek SM, Weinberg RJ, Calakos N, Wetsel WC, Feng G (2007) Cortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant mice. Nature. 448(7156):894-900.
- Feng D, Marshburn D, Jen D, Weinberg RJ, Taylor II RM, Burette A. (2007) Stepping into the Third Dimension. J. Neurosci. Nov 21; 27(47):12757-12760.
- Hung AY, Futai K, Sala C, Valtschanoff JG, Ryu J, Woodworth MA, Kidd FL, Sung CC, Miyakawa T, Bear MF, Weinberg RJ, Sheng M. (2008) Smaller dendritic spines, weaker synaptic transmission, but enhanced spatial learning in mice lacking Shank1. J Neurosci. 28(7):1697-708.
- Racz B, Weinberg RJ. (2008) Organization of the Arp2/3 complex in hippocampal spines. J Neurosci. 28(22):5654-9.
- Burette AC, Strehler EE, Weinberg RJ (2008) "Fast" plasma membrane calcium pump PMCA2a concentrates in GABAergic terminals in the adult rat brain. J Comp Neurol. Nov 24;512(4):500-513.
- Yashiro K, Riday TT, Condon KH, Roberts AC, Bernardo DR, Prakash R, Weinberg RJ, Ehlers MD, Philpot BD. (2009) Ube3a is required for experience-dependent maturation of the neocortex. Nat Neurosci. Jun;12(6):777-83.
- Joiner ML, Lisé MF, Yuen EY, Kam AY, Zhang M, Hall DD, Malik ZA, Qian H, Chen Y, Ulrich JD, Burette AC, Weinberg RJ, Law PY, El-Husseini A, Yan Z, Hell JW. (2010) Assembly of a beta2-adrenergic receptor--GluR1 signalling complex for localized cAMP signalling. EMBO J. Jan 20;29(2):482-95.
- Kelm MK, Weinberg RJ, Criswell HE, Breese GR. (2010) The PLC/IP 3 R/PKC pathway is required for ethanol-enhanced GABA release. Neuropharmacology. Jun;58(7):1179-86.
- Jacob AL, Jordan BA, Weinberg RJ. (2010) Organization of amyloid-beta protein precursor intracellular domain-associated protein-1 in the rat brain. J Comp Neurol. Aug 15;518(16):3221-36.
- Kenyon KA, Bushong EA, Mauer AS, Strehler EE, Weinberg RJ, Burette AC. (2010) Cellular and subcellular localization of the neuron-specific plasma membrane calcium ATPase PMCA1a in the rat brain. J Comp Neurol. Aug 15;518(16):3169-83.
- Burette AC, Strehler EE, Weinberg RJ. (2010) A plasma membrane Ca2+ ATPase isoform at the postsynaptic density. Neuroscience. Sep 1;169(3):987-93.
- Wang Q, Charych EI, Pulito VL, Lee JB, Graziane NM, Crozier RA, Revilla-Sanchez R, Kelly MP, Dunlop AJ, Murdoch H, Taylor N, Xie Y, Pausch M, Hayashi-Takagi A, Ishizuka K, Seshadri S, Bates B, Kariya K, Sawa A, Weinberg RJ, Moss SJ, Houslay MD, Yan Z, Brandon NJ. (2010) The psychiatric disease risk factors DISC1 and TNIK interact to regulate synapse composition and function. Mol Psychiatry. Sep 14. 2010;doi:10.1038/mp.2010.87.
- Larsen RS, Corlew RJ, Henson MA, Roberts AC, Mishina M, Watanabe M, Lipton SA, Nakanishi N, Pérez-Otaño I, Weinberg RJ, Philpot BD. (2011) NR3A-containing NMDARs promote neurotransmitter release and spike timing-dependent plasticity. Nat. Neurosci. Mar;14(3):338-44.
- Wang X, McCoy PA, Rodriguiz RM, Pan Y, Je HS, Roberts AC, Kim CJ, Berrios J, Colvin JS, Bousquet-Moore D, Lorenzo I, Wu G, Weinberg RJ, Ehlers MD, Philpot BD, Beaudet AL, Wetsel WC, Jiang YH. (2011) Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3. Hum. Mol. Genet. Aug 1;20(15):3093-108.
- Restituito S, Khatri L, Ninan I, Mathews PM, Liu X, Weinberg RJ, Ziff EB. (2011) Synaptic autoregulation by metalloproteases and γ-secretase. J Neurosci. Aug 24;31(34):12083-93.
- Burette AC, Weinberg RJ, Sassani P, Abuladze N, Kao L, Kurtz I. (2012) The sodium-driven chloride/bicarbonate exchanger in presynaptic terminals. J Comp Neurol. May 1;520(7):1481-92.
- Harris KM, Weinberg RJ. (2012) Ultrastructure of synapses in the mammalian brain. Cold Spring Harb Perspect Biol. May 1;4(5). pii: a005587. doi: 10.1101/cshperspect.a005587. Review.
- Wallace ML, Burette AC, Weinberg RJ, Philpot BD. (2012) Maternal loss of Ube3a produces an excitatory/inhibitory imbalance through neuron type-specific synaptic defects. Neuron. Jun 7;74(5):793-800.
- Burette AC, Lesperance T, Crum J, Martone M, Volkmann N, Ellisman MH, Weinberg RJ. (2012) Electron tomographic analysis of synaptic ultrastructure. J Comp Neurol. Aug 15;520(12):2697-711.
- Rácz B, Weinberg RJ. (2012) Microdomains in forebrain spines: al ultrastructural perspective. Mol Neurobiol. Feb;47(1):77-89. PMCID:PMC3538892
- Kunz PA, Burette AC, Weinberg RJ, Philpot BD. (2012) Glycine receptors support excitatory neurotransmitter release in developing mouse visual cortex. J Physiol. Nov 15;590(Pt 22):5749-64.
- Stephenson DT, Coskran TM Kelly MP, Kleiman RJ, Morton D, O'Neill SM, Schmidt CJ, Weinberg RJ, Menniti FS. (2012) The distribution of phosphodiesterase 2A in the rat brain. Neuroscience. Dec 13;226:145-55.