Neuronal cell types in the fly: single-cell anatomy meets single-cell genomics.

At around 150 000 neurons, the adult Drosophila melanogaster central nervous system is one of the largest species, for which a complete cellular catalogue is imminent. While numerically much simpler than mammalian brains, its complexity is still difficult to parse without grouping neurons into consistent types, which can number 1-1000 cells per hemisphere. We review how neuroanatomical and gene expression data are being used to discover neuronal types at scale. The correlation among multiple co-varying neuronal properties, including lineage, gene expression, morphology, connectivity, response properties and shared behavioral significance is essential to the definition of neuronal cell type. Initial studies comparing morphological and transcriptomic definitions of neuronal type suggest that these are highly consistent, but there is much to do to match these approaches brain-wide. Matched single-cell transcriptomic and morphological data provide an effective reference point to integrate other data types, including connectomics data. This will significantly enhance our ability to make functional predictions from brain wiring diagrams as well facilitating molecular genetic manipulation of neuronal types

The natverse, a versatile toolbox for combining and analysing neuroanatomical data.

To analyse neuron data at scale, neuroscientists expend substantial effort reading documentation, installing dependencies and moving between analysis and visualisation environments. To facilitate this, we have developed a suite of interoperable open-source R packages called the natverse. The natverse allows users to read local and remote data, perform popular analyses including visualisation and clustering and graph-theoretic analysis of neuronal branching. Unlike most tools, the natverse enables comparison across many neurons of morphology and connectivity after imaging or co-registration within a common template space. The natverse also enables transformations between different template spaces and imaging modalities. We demonstrate tools that integrate the vast majority of Drosophila neuroanatomical light microscopy and electron microscopy connectomic datasets. The natverse is an easy-to-use environment for neuroscientists to solve complex, large-scale analysis challenges as well as an open platform to create new code and packages to share with the community

Towards an integrated understanding of neural networks

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Mathematics, 2018.Cataloged from PDF version of thesis.Includes bibliographical references (pages 123-136).Neural networks underpin both biological intelligence and modern Al systems, yet there is relatively little theory for how the observed behavior of these networks arises. Even the connectivity of neurons within the brain remains largely unknown, and popular deep learning algorithms lack theoretical justification or reliability guarantees. This thesis aims towards a more rigorous understanding of neural networks. We characterize and, where possible, prove essential properties of neural algorithms: expressivity, learning, and robustness. We show how observed emergent behavior can arise from network dynamics, and we develop algorithms for learning more about the network structure of the brain.by David Rolnick.Ph. D

A connectome and analysis of the adult Drosophila central brain

The neural circuits responsible for animal behavior remain largely unknown. We summarize new methods and present the circuitry of a large fraction of the brain of the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses in, and proofread such large data sets. We define cell types, refine computational compartments, and provide an exhaustive atlas of cell examples and types, many of them novel. We provide detailed circuits consisting of neurons and their chemical synapses for most of the central brain. We make the data public and simplify access, reducing the effort needed to answer circuit questions, and provide procedures linking the neurons defined by our analysis with genetic reagents. Biologically, we examine distributions of connection strengths, neural motifs on different scales, electrical consequences of compartmentalization, and evidence that maximizing packing density is an important criterion in the evolution of the fly's brain