Yuriy Mishchenko Papers:
Mishchenko Y. (2011) "Reconstruction of complete connectivity matrix for connectomics by sampling neural connectivity with fluorescent synaptic markers.", Journal of Neuroscience Methods 196, 289

Physical organization of the nervous system is a topic of great interest in neuroscience. Although significant amount of knowledge about brain structures had been accumulated in the past, many details of nervous system organization and its role in animals? behavior remain obscure, while the problem of complete connectivity reconstructions has recently re-emerged as one of the major directions in modern neuroscience (i.e. connectomics). In this paper I talk about a novel paradigm for reconstructions of neural connectivity that can yield connectivity maps with high resolution, high speed of imaging, and robust and transparent data analysis. In essence, it is proposed that physical connectivity in a neural circuit can be sampled using anatomical fluorescent synaptic markers localized to different parts of the neural circuit with a technique for randomized genetic targeting such as Cre/Lox. High-resolution connectivity maps then can be extracted from particular datasets thus obtained. I describe in great detail how this approach can be implemented experimentally, and how neural connectivity matrix can be subsequently inferred statistically. I test utility of this approach on a simulated neural connectivity reconstruction experiments in C. elegans, a popular model organism in neuroscience, where real neural wiring diagram is available from serial electron microscopy. Using such actual wiring diagram, it turns out that complete connectivity matrix in C. elegans could be re-obtained with this approach in 1-7 days of imaging and data analysis, using existing genetic tools and off-the-shelf microscopy equipment. The best alternative connectomics approach of serial electron microscopy now would require at least 1-2 man-years for the same goal. I also talk about possible applications with different connectivity probes and genetic targeting techniques that can allow extending this approach to connectome reconstructions in larger organisms such as Drosophila. Full text