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Investigator

Benjamin H. White, Ph.D.

LMB
Building 35 Room 1B-1012
35 Convent Drive MSC4035
Bethesda MD 20892-4035
Office: (301) 435-5472
Lab: (301) 402-8658
Fax: (301) 402-0245
whiteb@intra.nimh.nih.gov

Dr. White heads the Section on Neural Function at NIMH. He received a B.A. in Physics and Mathematics from the University of Oregon (Honors College) and a Ph.D. in the Neural Sciences from Washington University in St. Louis. His graduate research and subsequent postdoctoral work at Yale University focused on mechanisms of ion channel gating and modulation. Shortly before he joined NIMH in 2002, his interests began to shift to using ion channels to manipulate neurons to investigate the brain substrates of behavior. Since coming to NIMH his laboratory has developed genetic tools for activating and suppressing targeted neurons in the fruitfly, Drosophila melanogaster, and sought to apply these tools to elucidate the neural circuit governing a developmentally essential behavioral program. This program, which governs the expansion of the wings at the end of metamorphosis, provides a simple paradigm for understanding how hormonal and environmental factors act to recruit motor patterns and assemble behavioral sequences. Because flies can choose when to expand their wings based on their environmental circumstances, this behavioral paradigm is also ideal for studying decision-making, the most fundamental aspect of behavioral integration.



While considerable progress has been made in understanding the molecular and cellular foundations of nervous system function, much less is known about the integrative processes that give rise to behavior. This situation is rapidly changing with the development of tools that allow nervous system activity to be monitored and manipulated in increasingly refined ways. Emerging tools for manipulation, in the form of genes that can be selectively expressed in subsets of neurons and whose products alter neuronal activity, are increasingly useful in mapping neuronal circuits in the fruit fly, where researchers have been able to take advantage of targeting techniques that afford reproducible, cell-type specific, and temporally restricted, expression of genes of interest. It is now possible to repeatedly turn on or off specific subsets of neurons in freely behaving flies.

My laboratory is actively engaged in generating and exploiting methods for the identification and analysis of neuronal circuits. In addition to previously developed tools for the suppression and enhancement of activity, we recently introduced a new tool for acutely activating neurons in response to small temperature shifts (see Peabody et al.,2009). We have also developed a general method for systematically restricting transgene expression to permit refined targeting of small subsets of neurons (Luan et al.,2006). The latter technique promises to permit the identification and characterization of neuronal circuits underlying behavior in unprecedented detail.

We are applying these methods to map the neuronal circuit underlying wing expansion, a hormonally-governed process that must be coordinated both with the emergence of the adult animal from the pupal case and with environmental conditions upon emergence. The mechanisms by which extrinsic and intrinsic factors act on neuronal networks to orchestrate a specific behavioral output are thus naturally open to investigation in this system. Because wing expansion is innate, its circuitry also must be laid down during development and identifying the developmental genes that specify this circuitry is a further goal of the research conducted in my laboratory.






Bursicon-expressing Neurons in Adult Drosophila

Components of the Wing Expansion Network


A fly's wings develop as compact, folded structures and must be expanded and hardened after metamorphosis to make them flight-worthy. Expansion is critical for the animal's survival and is governed by an innate, hormonally-governed program. This program is necessarily sensitive to the environment to insure that the animal does not try to expand its fragile wings in a place where they might be damaged prior to hardening. Extrinsic and intrinsic factors therefore interact to determine the animal's behavior after emergence.

The intrinsic factor most directly responsible for wing expansion is the hormone bursicon, which coordinates somatic physiological changes with the motor patterns of air swallowing and abdominal contraction to orchestrate wing expansion. The somatic and behavioral aspects of wing expansion are mediated by anatomically distinct populations of bursicon-expressing neurons (Peabody et al. (2008) J. Neurosci. 28:14379-91), shown in the above picture. In magenta are the "output" neurons located in the abdominal ganglion, which secrete the hormone into the blood to effect somatic changes. Secretion occurs at �neurohemal� release sites in the abdominal nerves, which are the densely stained magenta fibers exiting the abdominal ganglion at the bottom of the picture. (Because these fibers have been broken in this whole mount preparation, they then wrap up around the ventral nerve cord.) In white, are the two bursicon-secreting neurons of the subesophageal ganglion, which have been double-labeled with GFP. These neurons mediate the behavioral effects of bursicon.

Staff Image
  • 1) Diao, F. and White, B. H. (2012)
  • A Novel Approach for Directing Transgene Expression in Drosophila: T2A-Gal4 In-Frame Fusion.
  • Genetics, 190, 1139-1144
  • 2) Luan, H., Diao, F., Peabody, N. C., and White, B. H. (2012)
  • Command and compensation in a neuromodulatory decision network
  • J Neurosci, 32, 880-889
  • 3) Ting, C.Y., Gu, S., Guttikonda, S., Lin, T.Y., White B.H., Lee, C.-H. (2011)
  • Focusing Transgene Expression in Drosophila by Coupling Gal4 With a Novel Split-LexA Expression System
  • Genetics, 188, 229-33
  • 4) Peabody, N. C., Pohl, J. B., Diao, F., Vreede, A. P., Sandstrom, D. J., Wang, H., Zelensky, P. K., and White, B. H. (2009)
  • Characterization of the Decision Network for Wing Expansion in Drosophila Using Targeted Expression of the TRPM8 Channel.
  • J. Neurosci., 29, 3343–53
  • 5) White, B. H. and Peabody, N. C. (2009)
  • Neurotrapping: cellular screens to identify the neural substrates of behavior in Drosophila
  • Front Mol Neurosci, 2, 20 Epub Nov 2009 (doi:10.3389/neuro.02.020.2009).
  • 6) Krashes, M.J., DasGupta, S., Vreede, A., White, B., Armstrong, J.D., Waddell, S. (2009)
  • A Neural Circuit Mechanism Integrating Motivational State with Memory Expression in Drosophila
  • Cell, 139, 416-427
  • 7) Peabody, N. C., Diao, F., Luan, H., Wang, H., Dewey, E., Honegger, H-W., and White, B. H. (2008)
  • Bursicon Functions within the Drosophila Central Nervous System to Modulate Wing Expansion Behavior, Hormone Secretion, and Cell Death.
  • J. Neurosci., 28, 14379-91
  • 8) Gao, S., Takemura, S., Ting, C-Y., Huang, S., Lu, Z., Luan, H., Rister, J., Thum, A. S., Yang, M., Hong, S-T, Wang, J.W., Odenwald, W. F., White, B. H., Meinertzhagen, I. A., and Lee, C-H. (2008)
  • The Neural Substrate of Spectral Preference in Drosophila.
  • Neuron, 60, 328-42
  • 9) Luan, H and White, B.H. (2007)
  • Combinatorial Methods for Refined Neuronal Gene Targeting
  • Curr Opin Neurobiol , 17, 572-80
  • 10) Luan, H., Peabody, N.C., Vinson, C.R., and White B. H. (2006)
  • Refined Spatial Manipulation of Neuronal Function by Combinatorial Restriction of Transgene Expression.
  • Neuron, 52, 425-436
  • 11) Luan H, Lemon W. C., Peabody N, Pohl J. B., Zelensky P. K., Wang D, Nitabach M. N., Holmes T. C., and White B. H. (2006)
  • Functional Dissection of a Neuronal Network Required for Cuticle Tanning and Wing Expansion in Drosophila
  • Journal of Neuroscience, 26, 573-584
  • 12) Joiner, W.J., Crocker, A., White, B.H., and Sehgal A. (2006)
  • Sleep in Drosophila is regulated by adult mushroom bodies.
  • Nature, 441, 757-60
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