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George Spirou, PhD – Group Leader John W. and Jeannette S. Straton Research Chair in Neuroscience; Professor, Otolaryngology

304.293.3490

1 Medical Center Drive
321 Biomedical Research Center
PO Box 9303
Morgantown, WV 26506-9303


Affiliations

Otolaryngology; Rockefeller Neuroscience Institute

Graduate Training

PhD in Neuroscience, University of Florida

Fellowship

Department of Biomedical Engineering and Center for Hearing Sciences, Johns Hopkins University


Research Topics

Neural Development, Nanoscale Connectomics, Hearing

Auditory Development and Connectomics Laboratory

Our work is focused on development of neural and glial circuits of the auditory brainstem. We study their assembly during early development and their mature circuit structure and function. .

Laboratory Techniques

  • In vitro brain-slice physiology and pharmacology
    • Whole-cell current and voltage clamp
    • Fluorescence imaging, including Ca imaging
    • Single neuron biophysical and circuit models
    • Viral vector transduction of neurons and glia
  • Lattice light-sheet, 2-photon, superresolution, confocal imaging
  • Gene expression profiles of developing neurons and glia
    • Quantitative real-time PCR
    • Single-cell RNA sequencing
  • Serial blockface scanning electron microscopy to study
    • Structural transformations in the developing brain
    • Connectomes of mature auditory system
  • High resolution electron tomography study of nerve terminal and synapse structure
  • 3D Immersive Virtual Reality exploration of cell models

Neural Development

A key goal of our laboratory is to understand the sequence of assembly of low-level circuits of the auditory system, focused on the brainstem and its activation by the auditory nerve. We have developed a novel whole-head brain slice preparation to pursue this goal. We have revealed that the auditory nerve fibers can drive neurons of the medial nucleus of the trapezoid body by E17.5, ~1 day before birth. A main focus of our work is to characterize and explain neuronal and glial structural dynamics during formation of the calyx of Held, the largest nerve terminal in the mammalian brain. We also examine detailed structure of nerve terminals using electron tomography.

We also measure changes in gene expression profiles, in order to identify molecular signaling pathways that mediate changing tissue dynamics during neural circuit formation. We collaborate with Henrique von Gersdorff, Vollum Institute, on structure/function study of neurotransmission.

We collaborate with Henrique von Gersdorff, Vollum Institute, on structure/function studies of neurotransmission; Sam Young, University of Iowa, on viral vectors; Peter Mathers, WVU, for molecular embryology of brainstem development; and Jiang Qian, Johns Hopkins University and Jun Wan, Indiana University, for gene expression studies.

Connectomics

The second major focus of our work is to define and understand parallel processing pathways of the auditory brainstem. We begin by reconstructing the neurons and glia and their functional connections at nanoscale resolution using serial blockface scanning electron microscopy (SBEM) to image tissue volumes. Cells are reconstructed volumetrically, using manual and semi-automated techniques. Synapses are identified and exported for graph theoretical analysis, and neurons are transformed into a file format for simulation studies using NEURON. We collaborate with Eddie Fuller and CQ Zhang, WVU, for graph theory, Gianfranco Doretto, WVU, for computer vision and cell classification, Mark Culp, WVU, for multi-view statistical analysis, Mark Ellisman, UCSD, for SBEM imaging and with Paul Manis, UNC Chapel Hill, for neuron modeling.

New Tools for Neuroscience

We are developing technologies to visualize brain structures at cellular and sub cellular resolution using immersive virtual reality. Our current technology, syGlass (www.syglass.io), is a scientific data visualization and annotation system that works seamlessly with commercial VR technologies like the HTC Vive and Oculus Rift. We recently licensed syGlass from West Virginia University and began selling copies of the software. Our goal is to offer these powerful tools at a popular price so that every laboratory can have their own copy. With syGlass, high-resolution polygon meshes, 4D movies, and volumetric imaging data can be ingested quickly and easily, producing immersive VR renderings that provide new insight into data of all shapes and sizes. The syGlass project began as a collaboration between Drs. Spirou and Gianfranco Doretto (CSEE faculty), and computer science graduate student Michael Morehead, and led to the formation of the technology start-up company IstoVisio, Inc.

 

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Lab Personnel

Our lab members are drawn from biomedical and computer science graduate and undergraduate programs.

Doug KolsonDoug Kolson, PhD
Postdoctoral Fellow
dkolson@hsc.wvu.edu

Doug is a postdoctoral fellow in the Spirou lab. He completed his PhD in Neuroscience from WVU, and continues his research in neural development.

Paul Holcomb

Paul Holcomb
Neuroscience Graduate Student
pholcomb@mix.wvu.edu

Paul is a graduate student in the Spirou lab, studying the new field of connectomics.

Dakota Jackson

Dakota Jackson
Neuroscience Graduate Student
djacks14@mix.wvu.edu

Dakota is a graduate student in the Spirou lab, studying neural development.

Ashley Brandebura

Ashley Brandebura
Neuroscience Graduate Student
anbrandebura@mix.wvu.edu

Ashley is a graduate student in the Spirou lab, studying neural development.

Dan Heller

Dan Heller
Neuroscience Graduate Student
dth0003@mix.wvu.edu

Dan is a graduate student in the Spirou lab, studying neural development.

Computer Science and Statistics Team

Michael Morehead, MSMichael Morehead, MS
Computer Science Graduate Student
mmorehea@mix.wvu.edu

Michael is a computer science graduate student in the Spirou lab. He manages the 3D IVR laboratory, which studies connectomics.

Jad Ramadan

Jad Ramadan
Statistical Research Assistant
jramadan@hsc.wvu.edu

Jad is a statistical research assistant in the Spirou lab.

Nathan Spencer

Nathan Spencer
Computer Science Undergraduate Student

Nathan is a computer science undergraduate student in the Spirou lab, working on 3D immersive virtuality projects .

Mariah Dawson

Mariah Dawson
Bioinformatics Technician
mdawson@mix.wvu.edu

Mariah is the Connectomics Lab Manager for all cell tracing projects for the undergraduate students in the Spirou Lab.

Open Positions:

The Auditory Development and Connectomics Laboratory is currently seeking qualified individuals for the following positions:

Check back soon for available open positions.

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Publications

[2016]

  • Holcomb PS, Morehead M, Plaza S, Spirou GASemi-automated segmentation of cellular objects serial section electron microscopy images of the mouse auditory system. In Auditory and Vestibular Research: Methods and Protocols, 2nd edition, edited by B Sokolowski. Springer Press. 2016
  • Ryugo DR and Spirou GAGiant Synaptic Terminals: Endbulbs and Calyces of the Auditory System. In New Encyclopedia of Neuroscience, edited by LR Squire, TD Albright, FE Bloom, FH Gage, and NC Spitzer, Elsevier, Oxford, Great Britain, 2016
  • Holcomb PS, Morehead M, Doretto G, Chen P, Berg S, Plaza S, Spirou G. (2016) Rapid and Semi-automated Extraction of Neuronal Cell Bodies and Nuclei from Electron Microscopy Image Stacks. Methods Mol Biol, 1427: 277-90. PMCID: PMC4978130.
  • Kolson DR, Wan J, Wu J, Dehoff M, Brandebura AN, Qian J, Mathers PH,Spirou GTemporal patterns of gene expression during calyx of held development. Dev Neurobiol (2016 Feb) 76(2):166-89 [Epub 2015 Jul].

[2015]

  • Perkins GA, Jackson DR, Spirou GAResolving presynaptic structure by electron tomographySynapse (2015 May) 69(5):268-82. PMID:25683026.
  • Spirou GA, Jackson D, Perkins GA. Mitochondria Anchored at the Synapse. InThe Functions, Disease-Related Dysfunctions, and Therapeutic Targeting of Neuronal Mitochondria , edited by VK Gribkoff and EA Jonas. John Wiley and Sons, Hoboken, 2015.

[2013]

[2012]

  • Marrs GS, Spirou GAEmbryonic assembly of auditory circuits: spiral ganglion and brainstemJ Physiol (2012 May) 590(Pt 10):2391-408. doi: 10.1113/jphysiol.2011.226886.
  • Manis PB, Xie R, Wang Y, Marrs GS, Spirou GAThe Endbulb of Held. Invited review chapter in Springer Handbook of Auditory Research, edited by LO Trussell and AN Popper. Springer, New York, 2012.

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WVU Rockefeller Neuroscience Institute