Since the death of Robert Wenthold in October, 2009, the lab has continued to support the projects of some of the researchers who had moved to the lab of Dr. Katherine Roche in NINDS (Elizabeth Webber, Kai Chang, Takaaki Hirai, as well as Chan-Ying Zheng who transferred this year from the lab of Dr. Kachar), as well as Gail Seabold, who has continued to work mainly in the lab here, although her PI is Sharon Milgram from NHLBI. The lab has continued to do some neuron cell culture preparations as needed by these researchers. We also oversee maintenance of the JEOL 1010 transmission electron microscope and related equipment, as well as the Zeiss LSM710 laser confocal microscope and Leica Biowave System, which continue to be used here by some of these researchers. In addition, reviews of manuscripts, both of other researchers at NIDCD, and reviews requested by various journals, are performed regularly. Basically, work now is done as collaborations with PIs of other labs, and we will become a separate core facility in October, the beginning of the 2012 fiscal year. Our main obligation will be to facilitate the projects of other PIs in the NIDCD. Some of the collaborations here continue the work done in the lab of Dr. Wenthold on the trafficking of glutamate receptors and associated proteins of the neuronal synapse. However, as part of our commitment to helping NIDCD studies, the lab has become involved more and more in studies of development and pathology of the cochlea, and in the near future the lab plans to develop some work on central auditory function. The specific research projects that the lab has been involved in as collaborators this year are as follows: NIDCD A With researchers of the original Wenthold/NIDCD lab: 1) Completion of a study with Philip Wang and Stephan Brenowitz on NMDA receptors on neuronal growth cones, recently submitted. Performed EM analyses used in this study and also provided the cultured neurons. Now published in the Journal of Neuroscience. 2) Continued work on a SALM1 paper with Gail Seabold and Philip Wang. This is an adhesion protein associated with glutamate receptors at synapses. Performed EM analyses used in this study and provided the cultured neurons. This paper is in revision following review by the Journal of Biological Chemistry. (posters presented at meetings also) 3) Worked with Chan-Ying Zheng to complete a video method paper on FRAP of synaptic spines now published in the journal JoVE. 4) Worked with Chan-Ying Zheng to complete a paper as an addendum to the published paper on PSD-95 and SAP102. This addendum is now published in the journal Communicative &Integrative Biology. 5) The lead investigator was invited to write a review paper on MAGUK plasticity for The Neuroscientist, and enlisted the help of Chan-Ying Zheng, Gail Seabold and Martin Horak. This now is in press and is published on-line. NIDCD B With others at NIDCD: 1) Worked with Dabin Ren from the lab of Dr. Xin-Xing Gu to complete 2 separate EM studies of immunogold localization on bacteria associated with Otitis Media in children and respiratory infections, including COPD, in adults. One has now been published in the journal Vaccine. A second paper is in review. 2) Worked with researchers from the lab of Dr. Andy Griffith on a study of changes in the cochlea involving mutants associated with deafness. This paper is now in press in J. Clin. Inv. (posters presented at meetings also) 3) Trained and working with Kate Szarama from the labs of Drs. Matt Kelley and Richard Chadwick looking at the ultrastructural changes in the cochlea related to development and disease. One paper is in review and another will be submitted soon. (posters presented at meetings also) 4) Working with Helen May-Simera from the lab of Dr. Matt Kelley (in collaboration with Kate Szarama) on immunogold localization of kinocilium proteins in the developing cochlea. 5) Completed, as noted above, 3 projects/papers with Chan-Ying Zheng while she was associated with the lab of Dr. Kachar. 6) Involved in some preliminary studies of EM immunogold distribution with researchers in the lab of Dr. Tom Friedman. Especially involved in training and working with Inna Bellyantseva on EM techniques. 7) Working on collaboration with members of the lab of Dr. Paul Sieving on EM localization of a surface protein in the retina of experimental mice. 8) Providing thin sections for Dr. Bechara Kachar in ultrastructural studies of hair cells and the cochlea. 9) Advising Janaina Brusco from the lab of Dr. Bechara Kachar on an EM immunogold and 3D study of synapses of the amygdala. 10) Advising Taro Fujikawa from the lab of Dr. Bechara Kachar on a study of kainate glutamate receptors in the cochlea. 11) Planning immunoEM studies on the dorsal cochlear nucleus for the lab of Dr. Stephan Brenowitz. 12) Planning EM studies of inner ear with Dr. Doris Wus lab. With other NIH institutes: 6) Working on several studies of EM localization of sonic hedgehog and its receptors, patched and smoothened, with Drs. Pamela Yao and Mark Mattson of NIA. A first author paper now is in press in the Journal of Comparative Neurology. We also have another first author manuscript in review in the Journal of Comparative Neurology, and an addendum to the former paper and other studies are in preparation. (posters presented at meetings also) 1) Involved in 2 preliminary studies on mutations of proteins that affect the nervous system (including a mouse model for schizophrenia) with Drs. Jie-Min Jia and Song Jiao of NIMH (manuscript in preparation). 2) Worked with the lab of Dax Hoffman in NICHD on a potassium channel auxiliary subunit involved in synaptic integration and plasticity. Paper in press in the journal Neuron. With labs outside of NIH: 1) Worked with Dr. Jinhyun Kim of Janelia Farm Research Campus (HHMI), on EM immunolocalization of a protein in the synaptic cleft. A manuscript is in review. 2) Worked on EM immunogold contributions to 3 papers related to pain effects on neuronal plasticity of the spinal cord with Dr. Yuan-Xiang Tao of Johns Hopkins School of Medicine in Baltimore;these involve other collaborators such as Drs. Richard Huganir and Jeffrey Rothstein of Johns Hopkins, and D. Olga Kopach of the Bogomoletz Institute of Physiology in the Ukraine. All 3 papers are now published in the journals Anesthesiology, Molecular Pain, and Pain. 3) Working on an EM immungold studies of the brain of related to trafficking of glutamate and GABA receptors in mice with researchers in the laboratory of Richard Huganir of Johns Hopkins School of Medicine in Baltimore. 4) Working with researchers in the laboratory of Dr. Paul Worley of Johns Hopkins School of Medicine in Baltimore on EM immunogold studies of several proteins related to protein trafficking in neurons, including distributions in normal rats and knock-in mice. One paper involving Shank3 and NMDA receptors in a mouse model of Autism is now published in the journal Cell. Another paper is near acceptance in the journal Cell and concerns APP, presenilin, and Arc trafficking related to Alzheimers disease. 5) Worked with Dr. Jeff Erickson of LSU Health Sciences Center on some EM immunogold studies of synapse plasticity. 6) Worked with Dr. Youming Lu of LSU School of Medicine on ultrastructural changes in neurons related to signaling in synaptic transmission. A manuscript is in review. So far in 2011, the lab has published (or has in press) 11 papers, half of these within NIDCD, and has several other papers with NIDCD and other labs in review or final preparation that we hope to have in press by the end of 2011.

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National Institute on Deafness and Other Communication Disorders
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Petralia, Ronald S (2012) Distribution of extrasynaptic NMDA receptors on neurons. ScientificWorldJournal 2012:267120
Szarama, Katherine B; Gavara, NĂºria; Petralia, Ronald S et al. (2012) Cytoskeletal changes in actin and microtubules underlie the developing surface mechanical properties of sensory and supporting cells in the mouse cochlea. Development 139:2187-97
Yang, Ying; Shu, Xiaogang; Liu, Dan et al. (2012) EPAC null mutation impairs learning and social interactions via aberrant regulation of miR-124 and Zif268 translation. Neuron 73:774-88
Seabold, Gail K; Wang, Philip Y; Petralia, Ronald S et al. (2012) Dileucine and PDZ-binding motifs mediate synaptic adhesion-like molecule 1 (SALM1) trafficking in hippocampal neurons. J Biol Chem 287:4470-84
Petralia, Ronald S; Wang, Ya-Xian; Mattson, Mark P et al. (2012) Subcellular distribution of patched and smoothened in the cerebellar neurons. Cerebellum 11:972-81
Mitchell, Nicholas; Petralia, Ronald S; Currier, Duane G et al. (2012) Sonic hedgehog regulates presynaptic terminal size, ultrastructure and function in hippocampal neurons. J Cell Sci 125:4207-13
Standley, Steve; Petralia, Ronald S; Gravell, Manneth et al. (2012) Trafficking of the NMDAR2B receptor subunit distal cytoplasmic tail from endoplasmic reticulum to the synapse. PLoS One 7:e39585
Hu, Jia-Hua; Yang, Linlin; Kammermeier, Paul J et al. (2012) Preso1 dynamically regulates group I metabotropic glutamate receptors. Nat Neurosci 15:836-44
Wang, Philip Y; Petralia, Ronald S; Wang, Ya-Xian et al. (2011) Functional NMDA receptors at axonal growth cones of young hippocampal neurons. J Neurosci 31:9289-97
Sun, Wei; Maffie, Jon K; Lin, Lin et al. (2011) DPP6 establishes the A-type K(+) current gradient critical for the regulation of dendritic excitability in CA1 hippocampal neurons. Neuron 71:1102-15

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