Ronald S. Petralia and Ya-Xian Wang have run the Advanced Imaging Core facility of NIDCD since October 2011. This core is dedicated primarily to collaborating with and training other scientists in NIDCD in studies utilizing transmission electron microscopy (TEM). And we present an annual workshop on TEM as part of the EARssentials program. Some work also is done with other NIH institutes or outside NIH. In addition, Ronald Petralia regularly reviews papers for professional journals and reviews many various documents for NIDCD PIs, reviews grants, writes review papers and letters of recommendation, serves on several NIH committees and helps coordinate lab+office safety for NIDCD (including annual inspections and reports), and performs animal facility inspections as part of his duties in the ACUC. Lisa Cunningham lab: We are looking at effects of heat shock on the release/uptake of exosomes in the utricle. We are doing these studies in collaboration with the postBac IRTA fellow, Nora Welsh, and Andrew Breglio from the lab. Katie Kindt lab: The Core continues periodically to use TEM to study the hair cells and associated supporting cells of the zebrafish neuromasts and utricle. Recently, we published one study on a mutant affecting synaptic ribbon structure in neuromasts. We have another paper involving gap junctions in neuromasts, submitted to Nature Neuroscience. Paul Sieving/ Hongman Song/Ron Bush NIDCD/NEI: Our paper on Retinoschisin was published in Oct. 2016. We continue to perform new TEM studies of the retina associated with various mutant mice. Tom Friedman/Inna Belyantseva lab: We have a collaboration that will be submitted soon; we provided a detailed 3D analysis of stereocilia and rootlets associated with TrioBP mutants; and we performed or assisted with other TEM related to these studies. The Core continues to advise Inna Belyantseva on TEM techniques including tomography, to optimize ultrastructural studies of hair cells and stereocilia. We also assist Inna with tissue preparation, e.g., freeze substitution. Others: Last year, we had worked extensively on studies with Doris Wu, Sharda Yadav, and Kazuya Ono, to look at changes in TEM and SEM structure of stereocilia and kinocilia and the cuticular plate in the utricle of mutant mice. This year, we gave some limited assistance to Kazuya Ono; this may continue in the near future. Also, the Core continued to assist Robstein Chidavaenzi, a fellow in the lab of Bechara Kachar, until he left in June of this year, examining spectrins and associated proteins in stereocilia rootlets. We also provide some assistance to Willy Sun and Evan Krystofiak related to TEM and SEM. And our final study with Matt Kelley and Helen May-Simera was published in Oct. 2016. Other NIH institutes: NIA /Mark Mattson/Pamela Yao lab: We published a paper on effects of sonic hedgehog on mitochondria (with Jennifer Lippincott-Schwartz-now in Janelia Farms). In addition, we published review papers on sonic hedgehog and invaginating presynaptic terminals. We also have a research paper in review on neuronal purine enzymes. We continue to work on various studies of neuronal function. NIHMS Zheng Li/Kaizheng Duan: We recently began a study on mitophagy in the amygdala associated with social anxiety. NICHD Dax Hoffman/Lin Lin: We have done immunogold labeling for localization of DPP6, a potassium channel auxiliary protein with EM immunogold; we will submit a manuscript soon. NINDS Wei Lu/Wenyan Han/Jun Li: We participated in a study on two synaptic cell adhesion molecules associated with GABAergic synapse development in the hippocampus: manuscript in review. NINDS Katherine Roche/Richa Lomash lab: We have been using TEM to study neurolastin function. We are looking at structural changes in the neurons in the brain of the mutant. Others: We have continued to some extent our involvement with studies of Nahid Tayebi/Ellen Sidransky (NHGRI) and Jeff Diamond/Jun Zhang (NINDS). The Core also may work with Gail Seabold (formerly NIDCD/currently OITE), on SALM1 in the retina in collaboration with Florentina Soto (Wash. Univ. School of Medicine). Outside NIH: This Spring, we began a collaboration with Feng Yang and Zhonghua Hu (Lieber Inst. for Brain Devel./Johns Hopkins Med Campus) on genes associated with schizophrenia, examining effects on cultured hippocampal neurons and HEK293 cells. Gavin Rumbaugh/Massimiliano Aceti (Scripps Institute): We submitted a paper on function of Syngap1 for review, based on work that we did with them previously. We train/advise/prepare samples for TEM for Kazuyo Takeda (FDA/CBER/Micr. & Imag. Core), and we expect that this work will lead to collaborations/publications in the future. We also have been planning studies with Jaroslav Blahos (Inst. Exp. Med. ASCR/Czech Rep.) on distribution of a protein associated with synaptic cannabinoid receptors, and with Megan Wyeth (Stanford, CA) on studies of inhibitory neurons in the hippocampus. In addition to collaborations, Ron Petralia serves as a consultant on studies of T. Fujikawa (Japan)-GluRs in hair cell synapses.

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Deafness & Other Communication Disorders
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Takahashi, Satoe; Sun, Willy; Zhou, Yingjie et al. (2018) Prestin Contributes to Membrane Compartmentalization and Is Required for Normal Innervation of Outer Hair Cells. Front Cell Neurosci 12:211
Zhao, Jun; Krystofiak, Evan S; Ballesteros, Angela et al. (2018) Multiple claudin-claudin cis interfaces are required for tight junction strand formation and inherent flexibility. Commun Biol 1:50
Zhang, Qiuxiang; Li, Suna; Wong, Hiu-Tung C et al. (2018) Synaptically silent sensory hair cells in zebrafish are recruited after damage. Nat Commun 9:1388
Becker, Lars; Schnee, Michael E; Niwa, Mamiko et al. (2018) The presynaptic ribbon maintains vesicle populations at the hair cell afferent fiber synapse. Elife 7:
Petralia, Ronald S; Wang, Ya-Xian; Mattson, Mark P et al. (2018) Invaginating Structures in Mammalian Synapses. Front Synaptic Neurosci 10:4
Lin, Lin; Murphy, Jonathan G; Karlsson, Rose-Marie et al. (2018) DPP6 Loss Impacts Hippocampal Synaptic Development and Induces Behavioral Impairments in Recognition, Learning and Memory. Front Cell Neurosci 12:84
Williamson, Julie; Petralia, Ronald S; Wang, Ya-Xian et al. (2017) Purine Biosynthesis Enzymes in Hippocampal Neurons. Neuromolecular Med 19:518-524
Li, Jun; Han, Wenyan; Pelkey, Kenneth A et al. (2017) Molecular Dissection of Neuroligin 2 and Slitrk3 Reveals an Essential Framework for GABAergic Synapse Development. Neuron 96:808-826.e8
Sheets, Lavinia; He, Xinyi J; Olt, Jennifer et al. (2017) Enlargement of Ribbons in Zebrafish Hair Cells Increases Calcium Currents But Disrupts Afferent Spontaneous Activity and Timing of Stimulus Onset. J Neurosci 37:6299-6313
Yao, Pamela J; Manor, Uri; Petralia, Ronald S et al. (2017) Sonic hedgehog pathway activation increases mitochondrial abundance and activity in hippocampal neurons. Mol Biol Cell 28:387-395

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