Behavioral barcoding in the cloud: Embracing data-intensive digital phenotyping in neuropharmacology
ABSTRACT For decades, studying the behavioral effects of individual drugs and genetic mutations has been at the heart of efforts to understand and treat nervous system disorders. High-throughput technologies adapted from other disciplines (e.g., high-throughput chemical screening, genomics) are changing the scale of data acquisition in behavioral neuroscience. Massive behavioral datasets are beginning to emerge, particularly from zebrafish labs, where behavioral assays can be performed rapidly and reproducibly in 96-well, high-throughput format. Mining these datasets and making comparisons across different assays are major challenges for the field. Here, we review behavioral barcoding, a process by which complex behavioral assays are reduced to a string of numeric features, facilitating analysis and comparison within and across datasets.
- SourceAvailable from: Tjakko J Van Ham
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- "As mentioned in the introduction, the zebrafish has proven its value as a model in various aspects of neuroscience, however, these are beyond the scope of this review. Examples of these aspects include modeling behavior and complex behavioral brain disorders in adult zebrafish, optogenetics, understanding neurogenesis and neuroregeneration, as well as high throughput behavioral and neuroactive drug discovery (Baraban, 2007; Baraban et al., 2013; Chapouton et al., 2007; Kalueff et al., 2014b; Kokel et al., 2012; Kyritsis et al., 2014). "
ABSTRACT: A major question in research on immune responses in the brain is how the timing and nature of these responses influence physiology, pathogenesis or recovery from pathogenic processes. Proper understanding of the immune regulation of the human brain requires a detailed description of the function and activities of the immune cells in the brain. Zebrafish larvae allow long-term, noninvasive imaging inside the brain at high-spatiotemporal resolution using fluorescent transgenic reporters labeling specific cell populations. Together with recent additional technical advances this allows an unprecedented versatility and scope of future studies. Modeling of human physiology and pathology in zebrafish has already yielded relevant insights into cellular dynamics and function that can be translated to the human clinical situation. For instance, in vivo studies in the zebrafish have provided new insight into immune cell dynamics in granuloma formation in tuberculosis and the mechanisms involving treatment resistance. In this review, we highlight recent findings and novel tools paving the way for basic neuroimmunology research in the zebrafish. GLIA 2014. © 2014 Wiley Periodicals, Inc.Glia 05/2015; 63(5). DOI:10.1002/glia.22780 · 6.03 Impact Factor
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- "Zebrafish have emerged as versatile models of vertebrate biology, due to their amenability to genetic and pharmacological manipulations, optical transparency during embryogenesis and larval development, and facile and economical husbandry –. They have been used extensively to investigate the molecular and cellular mechanisms that contribute to tissue patterning  and more recently have contributed to our understanding of tissue regeneration, tumorigenesis, metabolism, infectious disease, and behavior –. As the importance of teleost models in biomedical research continues to grow, transgenic lines that can provide real-time indicators of specific biological events will be increasingly valuable. "
ABSTRACT: The Hedgehog (Hh) pathway is essential for embryonic development and tissue regeneration, and its dysregulation can lead to birth defects and tumorigenesis. Understanding how this signaling mechanism contributes to these processes would benefit from an ability to visualize Hedgehog pathway activity in live organisms, in real time, and with single-cell resolution. We report here the generation of transgenic zebrafish lines that express nuclear-localized mCherry fluorescent protein in a Gli transcription factor-dependent manner. As demonstrated by chemical and genetic perturbations, these lines faithfully report Hedgehog pathway state in individual cells and with high detection sensitivity. They will be valuable tools for studying dynamic Gli-dependent processes in vertebrates and for identifying new chemical and genetic regulators of the Hh pathway.PLoS ONE 07/2014; 9(7):e103661. DOI:10.1371/journal.pone.0103661 · 3.23 Impact Factor
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- "This may, in turn, decrease the risk for relapse and increase tobacco abstinence rates. With the advent of the validated behavioral screen described here, primed with initial drug evaluation data, the development of a high-throughput screening method for pharmacotherapeutic modifiers of nicotine and ethanol response is now warranted, and a number of studies have shown measuring larval locomotion is amenable to high throughput approaches , , . Moreover, exploiting this model to evaluate medications approved for human use by the FDA enables clinicians to study these medications in clinical trials without further preclinical safety testing. "
ABSTRACT: Cigarette smoking remains the most preventable cause of death and excess health care costs in the United States, and is a leading cause of death among alcoholics. Long-term tobacco abstinence rates are low, and pharmacotherapeutic options are limited. Repositioning medications approved by the U.S. Food and Drug Administration (FDA) may efficiently provide clinicians with new treatment options. We developed a drug-repositioning paradigm using larval zebrafish locomotion and established predictive clinical validity using FDA-approved smoking cessation therapeutics. We evaluated 39 physician-vetted medications for nicotine-induced locomotor activation blockade. We further evaluated candidate medications for altered ethanol response, as well as in combination with varenicline for nicotine-response attenuation. Six medications specifically inhibited the nicotine response. Among this set, apomorphine and topiramate blocked both nicotine and ethanol responses. Both positively interact with varenicline in the Bliss Independence test, indicating potential synergistic interactions suggesting these are candidates for translation into Phase II clinical trials for smoking cessation.PLoS ONE 03/2014; 9(3):e90467. DOI:10.1371/journal.pone.0090467 · 3.23 Impact Factor