Strategies for identifying exact structure of neural circuits with broad light microscopy connectivity probes

摘要: Dissecting the structure of neural circuits in brain is one central problems neuroscience. Until present day, only way to obtain complete and detailed reconstructions was thought be serial section Electron Microscopy, which could take decades a small circuit. In this paper, we develop mathematical framework that allows performing such much faster cheaper with existing light microscopy genetic tools. framework, collection genetically targeted probes connectivity prepared from different animals then used systematically deduce circuit's connectivity. Each measurement represented as constraint on circuit architecture. Such constraints are computationally combined identify matrix for probed Connectivity here understood broadly, between identifiable neurons or classes neurons, etc. This paradigm may applied ChR2-assisted mapping, GRASP transsynaptic viruses, targeting techniques Brainbow, MARCM/MADM UAS/Gal4, model organisms C. Elegans, Drosophila, zerbafish, mouse, particular, demonstrate how, by using paradigm, wiring diagram all Elegans reconstructed Brainbow off-the-shelf tools time span week less. Described approach recovering exact even if not individually ~Np*log(N) (Np number nonzero entries N size matrix). For comparison, minimal would necessary determine directly probing connections individual when knows a-priory pairs should tested, e.g. whole-cell patches, ~Np.