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Neuronal networks are high-dimensional graphs that are packed into three-dimensional nervous tissue at extremely high density. Comprehensively mapping these networks is therefore a major challenge. Although recent developments in volume electron microscopy imaging have made data acquisition feasible for circuits comprising a few hundreds to a few thousands of neurons, data analysis is massively lagging behind. The aim of this Perspective is to summarize and quantify the challenges for data analysis in cellular-resolution connectomics and describe current solutions involving online crowd-sourcing and machine-learning approaches.
At macroscopic scales, the human connectome comprises anatomically distinct brain areas, the structural pathways connecting them and their functional interactions. Annotation of phenotypic associations with variation in the connectome and cataloging of neurophenotypes promise to transform our understanding of the human brain. In this Review, we provide a survey of magnetic resonance imaging–based measurements of functional and structural connectivity. We highlight emerging areas of development and inquiry and emphasize the importance of integrating structural and functional perspectives on brain architecture.
In this Historical Perspective, we ask what information is needed beyond connectivity diagrams to understand the function of nervous systems. Informed by invertebrate circuits whose connectivities are known, we highlight the importance of neuronal dynamics and neuromodulation, and the existence of parallel circuits. The vertebrate retina has these features in common with invertebrate circuits, suggesting that they are general across animals. Comparisons across these systems suggest approaches to study the functional organization of large circuits based on existing knowledge of small circuits.
The beginning of the 21st century has seen a renaissance in light microscopy and anatomical tract tracing that together are rapidly advancing our understanding of the form and function of neuronal circuits. The introduction of instruments for automated imaging of whole mouse brains, new cell type–specific and trans-synaptic tracers, and computational methods for handling the whole-brain data sets has opened the door to neuroanatomical studies at an unprecedented scale. We present an overview of the present state and future opportunities in charting long-range and local connectivity in the entire mouse brain and in linking brain circuits to function.
Zinc-finger DNA-binding domains are expressed on the surface of cells so that the cells can be tagged with fluorescently labeled oligonucleotides, enabling many possible applications in complex cell populations.
A two-laboratory study of the reproducibility of affinity purification–mass spectrometry shows that a standardized protocol results in highly reproducible interactome data.
Classic gene targeting and gene replacement can now be achieved in zebrafish after cleaving the genome with engineered nucleases in the presence of donor DNA. This simple-to-implement method enables new classes of biological study in this important model organism.
A review of zymography techniques is presented. Zymography approaches yield valuable information about enzyme forms and localization of activity in tissues or in whole organisms.
Classification of proteins by ligand binding similarity offers an alternative approach to evolutionary methods for organizing and understanding biology, allowing new insights into protein function and physiological signal transduction.
A fully automated pipeline that systematically models three-dimensional (3D) structural details of protein interactions will allow researchers to interpret perturbation effects within protein pathways and networks.
