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George Spirou, PhD - Director, Group Leader

John W. and Jeannette S. Straton Research Chair in Neuroscience; Director, Centers for Neuroscience; Professor, Otolaryngology

Dr. George Spirou

304.293.3490

Research Topics: Neural Development, Nanoscale Connectomics, Hearing

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.

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TopResearch Interests | Lab Personnel | Open Positions | Publications

Affiliations

Otolaryngology; Centers for Neuroscience

Graduate Training

Ph.D. in Neuroscience, University of Florida

Fellowship

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


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 

Journal of Neuroscience video cover

  • 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
  • 2-photon, superresolution, confocal imaging
  • Gene expression profiles of developing neurons and glia
    • Quantitative real-time PCR
    • Next-Gen 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 generate action potentials by embryonic day (E) 14.5 and can drive synaptically neurons of the ventral cochlear nucleus (VCN) by E15.5 (see figure). By E17.5, ~1 day before birth, stimulation of the auditory nerve can elicit action potentials in the contralateral medial nucleus of the trapezoid body, indicating very early formation of synaptic connections.

Whole-head brain slice

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.


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 Mark Ellisman, UCSD, for SBEM imaging and with Paul Manis, UNC Chapel Hill, for neuron modeling.

3D cellular field of MNTB


Visualization of Brain Structure

We are developing technologies to visualize brain structure at cellular and subcellular resolution using immersive virtual reality. Current technology uses a CAVE (CAVE Automated Virtual Environment) built from 3D TV screens so that multiple investigators can simultaneously view and discuss cellular scenes. This project is a collaboration amoung computer science, biomedical engineering, and neuroscience trainees, and is co-directed by Dr. Gianfranco Doretto, a faculty member in CSEE.

BrainTrek  

tablet and wand

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Lab Personnel

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

Doug Kolson

Doug 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. 




Michael Morehead, MS

Michael 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 VR laboratory, which studies connectomics.


Quinn Jones

Quinn Jones
Computer Science Graduate Student
qjones1@mix.wvu.edu

Quinn is a computer science graduate student in the Spirou lab.


Stas Pidhorskyi

Stanislav Pidhorskyi
Computer Science Graduate Student
stpidhorskyi@mix.wvu.edu

Stas is a computer science graduate student in the Spirou lab.




Jordan Brack

Jordan Brack
Computer Science Undergraduate Student
jabrack@mix.wvu.edu

Jordan is a computer science undergraduate student in the Spirou lab.




Jenn Nguyen

Jenn Nguyen
Computer Science Undergraduate Student
jqnguyen@mix.wvu.edu

Jenn is a computer science undergraduate student in the Spirou lab.



Haofan Zheng

Haofan Zheng
Computer Science Undergraduate Student
hazheng@mix.wvu.edu

Haofan is a computer science undergraduate student in the Spirou lab.





Open Positions:

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

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Publications

[2016]

  • Holcomb PS, Morehead M, Plaza S, Spirou GA. Semi-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 GA. Giant 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
  • Kolson DR, Wan J, Wu J, Dehoff M, Brandebura AN, Qian J, Mathers PH, Spirou G. Temporal 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 GA. Resolving presynaptic structure by electron tomography. Synapse (2015 May) 69(5):268-82. PMID:25683026.
  • Spirou GA, Jackson D, Perkins GA. Mitochondria Anchored at the Synapse. In The 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 GA. Embryonic assembly of auditory circuits: spiral ganglion and brainstem. J Physiol (2012 May) 590(Pt 10):2391-408. doi: 10.1113/jphysiol.2011.226886.
  • Manis PB, Xie R, Wang Y, Marrs GS, Spirou GA. The 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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