Genetic Dissection of Neural Circuits

Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
Neuron (Impact Factor: 15.05). 04/2008; 57(5):634-60. DOI: 10.1016/j.neuron.2008.01.002
Source: PubMed


Understanding the principles of information processing in neural circuits requires systematic characterization of the participating cell types and their connections, and the ability to measure and perturb their activity. Genetic approaches promise to bring experimental access to complex neural systems, including genetic stalwarts such as the fly and mouse, but also to nongenetic systems such as primates. Together with anatomical and physiological methods, cell-type-specific expression of protein markers and sensors and transducers will be critical to construct circuit diagrams and to measure the activity of genetically defined neurons. Inactivation and activation of genetically defined cell types will establish causal relationships between activity in specific groups of neurons, circuit function, and animal behavior. Genetic analysis thus promises to reveal the logic of the neural circuits in complex brains that guide behaviors. Here we review progress in the genetic analysis of neural circuits and discuss directions for future research and development.

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    • "For example, promoter-based strategies, coupled with viral tropism, have enabled selective expression of opsins in pyramidal neurons (Han et al., 2009), and viral approaches have also been used to achieve pathway selective blocking of neural transmission (Kinoshita et al., 2012). Notwithstanding these successes, these procedures have not provided a generally applicable means of achieving cell-type-specific transgene expression (Luo et al., 2008). However, several key advances have occurred, including the development of new genome editing tools (ZFNs, TALENs, the CRISPR/Cas9 system), demonstration of germline transmission of a transgene in the common marmoset (Sasaki et al., 2009), and the complete sequencing of the marmoset genome (Marmoset Genome Sequencing and Analysis Consortium, 2014). "

    Full-text · Article · Aug 2015 · Neuron
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    • "Therefore, achieving refined circuits remains a common challenge and goal for both vertebrate and invertebrate neuroscientists. The encouraging news is the unprecedented rapid advents in modern in vivo genetic and molecular techniques for fine mapping of neural circuits (Luo et al. 2008; Simpson 2009; White and Peabody 2009; Fore and Zhang 2013). In this review, we will discuss currently available tools for studying the structure and function of the nervous system, with a focus on intersectional strategies in Drosophila melanogaster. "
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    ABSTRACT: Understanding behavior requires unraveling the mysteries of neurons, glia, and their extensive connectivity. Drosophila has emerged as an excellent organism for studying the neural basis of behavior. This can be largely attributed to the extensive effort of the fly community to develop numerous sophisticated genetic tools for visualizing, mapping, and manipulating behavioral circuits. Here, we attempt to highlight some of the new reagents, techniques and approaches available for dissecting behavioral circuits in Drosophila. We focus on detailing intersectional strategies such as the Flippase-induced intersectional Gal80/Gal4 repression (FINGR), because of the tremendous potential they possess for mapping the minimal number of cells required for a particular behavior. The logic and strategies outlined in this review should have broad applications for other genetic model organisms.
    Full-text · Article · Apr 2015 · Journal of Comparative Physiology
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    • "Recapitulating endogenous gene expression is key to cell typespecific study (Luo et al., 2008) and can be achieved by standard , bacterial artificial chromosome (BAC) (Heintz, 2001; Ting and Feng, 2014), and site-directed transgenic methods. Standard and BAC transgenic methods both rely on random integration , which may help to study interneuron subpopulations that express the same cis-regulatory elements. "
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    ABSTRACT: The evolution of genetically targeted tools has begun to allow us to dissect anatomically and functionally heterogeneous interneurons, and to probe circuit function from synapses to behavior. Over the last decade, these tools have been used widely to visualize neurons in a cell type-specific manner, and engage them to activate and inactivate with exquisite precision. In this process, we have expanded our understanding of interneuron diversity, their functional connectivity, and how selective inhibitory circuits contribute to behavior. Here we discuss the relative assets of genetically encoded fluorescent proteins (FPs), viral tracing methods, optogenetics, chemical genetics, and biosensors in the study of inhibitory interneurons and their respective circuits.
    Full-text · Article · Oct 2014 · Frontiers in Neural Circuits
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