Principal Investigator: Benjamin White
Section on Neural Function
Laboratory of Molecular Biology
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 increasingly refined tools for monitoring and manipulating nervous system activity. Transgenes that can be selectively expressed in subsets of neurons, and whose products alter electrical or synaptic activity, are increasingly exploited to map neuronal circuits in the fruit fly, Drosophila melanogaster. These efforts are supported by targeting techniques that afford reproducible, cell-type specific, and temporally restricted, expression of transgenes. Using these techniques in combination, it is now routinely possible turn on or off very specific subsets of neurons in freely behaving flies.
My laboratory is actively engaged in generating tools for the identification and analysis of neuronal circuits. We have developed techniques for the constitutive suppression (White et. al., 2001) and enhancement of neuronal excitability (Luan, Lemon et al., 2006; Nitabach et al. 2006), as well as a tool for acutely activating neurons in response to small temperature shifts (Peabody et al.,2009). We have also developed general methods for targeting genetic manipulations to cell types of interest. These include the Split Gal4 system (Luan et al.,2006), which permits refined targeting of transgenes to small subsets of neurons, and the T2A-Gal4 In-Frame-Fusion method (Diao and White, 2012), which can target neurons that express a given gene of interest.
We are applying these methods to map the neuronal circuit underlying wing expansion, a hormonally-governed process that must be coordinated with environmental conditions. The mechanisms by which extrinsic and intrinsic factors modulate behavioral decisions are naturally open to investigation in this system and our goal is to understand how both internal and external cues are processed to produce specific motor outputs. 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.
Command and Compensation in a Neuromodulatory Decision Network. Luan H, Diao F, Peabody NC, White BH. J Neurosci. 2012 Jan 18;32(3):880-9. doi: 10.1523/JNEUROSCI.3707-11.2012. PMID: 22262886.
A novel approach for directing transgene expression in Drosophila: T2A-Gal4 in-frame fusion. Diao F, White BH. Genetics. 2012 Mar;190(3):1139-44. doi: 10.1534/genetics.111.136291. Epub 2011 Dec 29. PMID: 22209908.
Focusing transgene expression in Drosophila by coupling Gal4 with a novel split-LexA expression system. Ting CY, Gu S, Guttikonda S, Lin TY, White BH, Lee CH. Genetics. 2011 May;188(1):229-33. doi: 10.1534/genetics.110.126193. Epub 2011 Mar 2. PMID: 21368278.
Characterization of the decision network for wing expansion in Drosophila using targeted expression of the TRPM8 channel. Peabody NC, Pohl JB, Diao F, Vreede AP, Sandstrom DJ, Wang H, Zelensky PK, White BH. J Neurosci. 2009 Mar 18;29(11):3343-53. doi: 10.1523/JNEUROSCI.4241-08.2009. PMID: 19295141.
A neural circuit mechanism integrating motivational state with memory expression in Drosophila. Krashes MJ, DasGupta S, Vreede A, White B, Armstrong JD, Waddell S. Cell. 2009 Oct 16;139(2):416-27. doi: 10.1016/j.cell.2009.08.035. PMID: 19837040.
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