Molecular topography of an entire nervous system.

We acquired a rapidly preserved human surgical sample from the temporal lobe of the cerebral cortex. We stained a 1 mm3 volume with heavy metals, embedded it in resin, cut more than 5000 slices at ~30 nm and imaged these sections using a high-speed multibeam scanning electron microscope. We used computational methods to render the three-dimensional structure containing 57,216 cells, hundreds of millions of neurites and 133.7 million synaptic connections. The 1.4 petabyte electron microscopy volume, the segmented cells, cell parts, blood vessels, myelin, inhibitory and excitatory synapses, and 104 manually proofread cells are available to peruse online. Many interesting and unusual features were evident in this dataset. Glia outnumbered neurons 2:1 and oligodendrocytes were the most common cell type in the volume. Excitatory spiny neurons comprised 69% of the neuronal population, and excitatory synapses also were in the majority (76%). The synaptic drive onto spiny neurons was biased more strongly toward excitation (70%) than was the case for inhibitory interneurons (48%). Despite incompleteness of the automated segmentation caused by split and merge errors, we could automatically generate (and then validate) connections between most of the excitatory and inhibitory neuron types both within and between layers. In studying these neurons we found that deep layer excitatory cell types can be classified into new subsets, based on structural and connectivity differences, and that chandelier interneurons not only innervate excitatory neuron initial segments as previously described, but also each others initial segments. Furthermore, among the thousands of weak connections established on each neuron, there exist rarer highly powerful axonal inputs that establish multi-synaptic contacts (up to ~20 synapses) with target neurons. Our analysis indicates that these strong inputs are specific, and allow small numbers of axons to have an outsized role in the activity of some of their postsynaptic partners.

/pdf/a-connectomic-study-of-a-petascale-fragment-of-human-26776rd78e.pdf

A connectomic study of a petascale fragment of human cerebral cortex

Brains contain networks of interconnected neurons, so knowing the network architecture is essential for understanding brain function. We therefore mapped the synaptic-resolution connectome of an insect brain (Drosophila larva) with rich behavior, including learning, value-computation, and action-selection, comprising 3,013 neurons and 544,000 synapses. We characterized neuron-types, hubs, feedforward and feedback pathways, and cross-hemisphere and brain-nerve cord interactions. We found pervasive multisensory and interhemispheric integration, highly recurrent architecture, abundant feedback from descending neurons, and multiple novel circuit motifs. The brain’s most recurrent circuits comprised the input and output neurons of the learning center. Some structural features, including multilayer shortcuts and nested recurrent loops, resembled powerful machine learning architectures. The identified brain architecture provides a basis for future experimental and theoretical studies of neural circuits. One-Sentence Summary We generated a synaptic-resolution brain connectome and characterized its connection types, neuron types, and circuit motifs.

The connectome of an insect brain

What is a cell type and how to define it?

SNT is an end-to-end framework for neuronal morphometry and whole-brain connectomics that supports tracing, proof-editing, visualization, quantification and modeling of neuroanatomy. With an open architecture, a large user base, community-based documentation, support for complex imagery and several model organisms, SNT is a flexible resource for the broad neuroscience community. SNT is both a desktop application and multi-language scripting library, and it is available through the Fiji distribution of ImageJ.

/pdf/snt-a-unifying-toolbox-for-quantification-of-neuronal-79c3kt1ccc.pdf

SNT: a unifying toolbox for quantification of neuronal anatomy

An animal’s nervous system changes as its body grows from birth to adulthood and its behaviours mature1–8. The form and extent of circuit remodelling across the connectome is unknown3,9–15. Here we used serial-section electron microscopy to reconstruct the full brain of eight isogenic Caenorhabditis elegans individuals across postnatal stages to investigate how it changes with age. The overall geometry of the brain is preserved from birth to adulthood, but substantial changes in chemical synaptic connectivity emerge on this consistent scaffold. Comparing connectomes between individuals reveals substantial differences in connectivity that make each brain partly unique. Comparing connectomes across maturation reveals consistent wiring changes between different neurons. These changes alter the strength of existing connections and create new connections. Collective changes in the network alter information processing. During development, the central decision-making circuitry is maintained, whereas sensory and motor pathways substantially remodel. With age, the brain becomes progressively more feedforward and discernibly modular. Thus developmental connectomics reveals principles that underlie brain maturation. Serial-section electron microscopy is used to reconstruct the full brain connectome of eight individual Caenorhabditis elegans at various stages of development, providing insight into the principles underlying brain maturation.

Connectomes across development reveal principles of brain maturation

From birth to adulthood, an animal9s nervous system changes as its body grows and its behaviours mature. The form and extent of circuit remodelling across the connectome is unknown. We used serial-section electron microscopy to reconstruct the full brain of eight isogenic C. elegans individuals across postnatal stages to learn how it changes with age. The overall geometry of the brain is preserved from birth to adulthood. Upon this constant scaffold, substantial changes in chemical synaptic connectivity emerge. Comparing connectomes among individuals reveals substantial connectivity differences that make each brain partly unique. Comparing connectomes across maturation reveals consistent wiring changes between different neurons. These changes alter the strength of existing connections and create new connections. Collective changes in the network alter information processing. Over development, the central decision-making circuitry is maintained whereas sensory and motor pathways substantially remodel. With age, the brain progressively becomes more feedforward and discernibly modular. Developmental connectomics reveals principles that underlie brain maturation.

/pdf/connectomes-across-development-reveal-principles-of-brain-5b2bsld1q3.pdf

From birth to adulthood, an animal’s nervous system changes as its body grows and its behaviours mature. However, the extent of circuit remodeling across the connectome is poorly understood. Here, we used serial-section electron microscopy to reconstruct the brain of eight isogenic C. elegans individuals at different ages to learn how an entire wiring diagram changes with maturation. We found that the overall shape of the nervous system is preserved from birth to adulthood, establishing a constant scaffold upon which synaptic change is built. We observed substantial connectivity differences among individuals that make each brain partly unique. We also observed developmental synaptic changes that are consistent between animals but different among neurons, altering the strengths of existing connections and creating additional connections. Collective synaptic changes alter information processing of the brain. Across maturation, the decision-making circuitry is maintained whereas sensory and motor pathways are substantially remodelled, and the brain becomes progressively more modular and feedforward. These synaptic changes reveal principles by which maturation shapes brain and behavior across development.

/pdf/connectomes-across-development-reveal-principles-of-brain-1cf2z23bge.pdf

Connectomes across development reveal principles of brain maturation in C. elegans

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Connectomes across development reveal principles of brain maturation

Connectomes across development reveal principles of brain maturation

Connectomes across development reveal principles of brain maturation in C. elegans