Timothy E. Holy, Ph.D.

Alan A. and Edith L. Wolff Professor

Neurosciences Program
Computational and Systems Biology Program

  • 314-362-0086

  • 314-362-0089

  • 314-362-4461

  • 4401 North Building

  • holy@wustl.edu

  • http://holylab.wustl.edu

  • calcium imaging, physiology, mathematical modeling, behavior, neurobiology, smell, olfaction, pheromones, neuroendocrine, circuits

  • Sensory processing and plasticity (olfaction), large-population calcium imaging, computation, social communication

Research Abstract:

We focus on three major areas: (1) studying the neural mechanisms of sensory perception, specifically detecting, recognizing, and remembering odorants, (2) developing and leveraging new methods for calcium imaging and cell type identification, and (3) development of new computational tools. We also investigate vocal communication and its disorders in mice.

We are attracted to the olfactory system first because of its brevity: phenomena like plasticity and recognition appear to happen at very early stages of the neuronal pathway. With a nearly exhaustive understanding of the inputs to a circuit, it becomes much more tractable to develop a crisp and quantitative understanding of the transformations performed by downstream circuitry. Second, we exploit the fact that mice exhibit a wide range of innate and trained behaviors that can be triggered by odorants; using odorants we and others have succeeded in getting mice to perform tasks that formerly were only in the domain of primate neuroscience.

In terms of techniques, we focus primarily on advancing microscopy and calcium imaging. My laboratory was the first to routinely record from tens of thousands of neurons simultaneously: we were among the independent inventors of light sheet microscopy, a fluorescence imaging technique for which our implementation was the first to perform fast three-dimensional imaging in large volumes of intact tissue. We are continuing our work in developing new imaging approaches and extending into combining optical methods with tools for molecular characterization of individual neurons.

In terms of computation, we are among the leading developers of a new programming language called Julia, a language similar to Matlab and Python but with the performance of C. We are leveraging Julia to develop new algorithms for neuronal network and image analysis.

Finally, we are analyzing vocal communication in mice as a model system for motor behavior and communication disorders.

Selected Publications:

Lee D, Kume M, Holy TE (2019). Sensory coding mechanisms revealed by optical tagging of physiologically defined neuronal types. Science 366: 1384-1389.

Greer CJ, Holy TE (2019). Fast objective coupled planar illumination microscopy. Nat Commun. 2019 10: 4483.

Holy TE (2018). The Accessory Olfactory System: Innately Specialized or Microcosm of Mammalian Circuitry? Annu Rev Neurosci. 41:501-525.

Xu PS, Lee D, Holy TE. (2016) Experience-Dependent Plasticity Drives Individua(6276)l Differences in Pheromone-Sensing Neurons. Neuron 91:878-892.

Barnes TD, Wozniak DF, Gutierrez J, Han TU, Drayna D, Holy TE. (2016) A Mutation Associated with Stuttering Alters Mouse Pup Ultrasonic Vocalizations. Curr Biol. pii: S0960-9822(16)30179-8.

Liang X, Holy TE, Taghert PH. Synchronous Drosophila circadian pacemakers display nonsynchronous Ca²⁺ rhythms in vivo. (2016)
Science. 351: 976-81

Fu X., Yan Y., Xu P. S, Geerlof-Vidavsky I., Chong W., Gross M. L., and Holy T. E. (2015) A molecular code for identity in the vomeronasal system. Cell 163: 1-11.

Hammen G. F., Turaga D., Holy T. E.*, and Meeks J. P.* (2014) Functional organization of glomerular maps in the mouse accessory olfactory bulb. Nature Neurosci 17: 953-961.

Turaga D. and Holy T.E. (2012) Organization of vomeronasal sensory coding revealed by fast volumetric calcium imaging. J. Neurosci. 32: 1612-1621.

Meeks JP, Arnson HA, and Holy TE. Representation and transformation of chemosensory information in the mouse accessory olfactory system. Nature Neuroscience 2010 13: 723-730.

Nodari F, Hsu F-F, Fu X, Holekamp TF, Kao L-F, Turk J, Holy TE. Sulfated steroids as natural ligands of mouse pheromone-sensing neurons. J. Neuroscience 2008 28: 6407-6418.

Holekamp TF, Turaga D, Holy TE. Fast three-dimensional fluorescence imaging of activity in neural populations by objective-coupled planar illumination microscopy. Neuron 2008 57: 661-672.

Holy T.E., Guo Z. (2005) Ultrasonic songs of male mice. PLoS Biology 3: e386.

Last Updated: 12/17/2019 3:41:47 PM

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