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Developmental Biology - Brain Development

Mouse Brain Has Billions of Synaptic Connections

Researchers identify the connections across all neurons in every region of the neocortex...

A comprehensive snapshot of the connectome or map of all brain neural connections, has so far only been accomplished for tiny areas of the brain, smaller than the head of a pin.

Larger brain volumes, such as long-range connectivity formed by bundles of extremely thin and long fibers, has only been studied in small numbers of individual neurons. Alternatively, studied at the macro-scale the connectome is only a 'zoomed-out' view of brain features without single-cell resolution. Neither giving a very complete picture of the brain.
The structure of synaptic connections between neurons shapes their activity and function.

In a paper published in Nature Communications, Blue Brain researchers show their trick lies in combining these two views. By integrating data from two recent datasets — the Allen Mouse Brain Connectivity Atlas and Janelia MouseLight — Blue Brain researchers identified some of the key rules dictating which individual neurons can form connections over large distances within the neocortex. This was possible as the two datasets complement each other throughout the entirety of the neocortex.

Complex Single-cell Resolution

Building on their previous work modelling local brain circuits, Blue Brain researchers recreated image parameters based on principles of neocortical connections to generate statistical compatibility between the two maps.

When studying the structure they built, they found something fascinating. At cell level resolution, the complex structure — previously only seen by neighboring neurons — now ties together neurons from different brain regions and opposite ends of the brain.
The discovery supports the rule of self-similarity previously documented in the human brain (from MRI data) and predicts that same rule applies to all levels of individual neurons.

Explains lead researcher of the Blue Brain Project - Michael W. Reimann PhD: "They [neurons] have been depicted as blunt cables, connecting or synchronizing whole brain regions. But maybe there is more to them — more specific targeting of individual neurons. This is what we learned from just a few, relatively course-grained principles, I expect with improved methods we will find more in the future."

Open Connectome A Powerful Model to Compare Findings.

According to Reimann, at this time additional constraints are unknown, but likely to exist. But, to start the process of refining their work, the model and data are now available to the public and can be found at the Blue Brain Mouse whole-neocortex connectome model.

This openly accessible connectome can serve as a powerful null model on which to compare experimental findings, as well as a substrate for whole-brain simulations of detailed neural networks.

Advancing the Case for Simulation

The simulation method allows scientists to target volumes orders of magnitude smaller than possible with experimental methods. Going forward, it will allow simulation of electrical activity in individual neurons, and at some point the entire neocortex.
"The findings enable us continue our simulation experiments at an exponentially increasing rate, meaning we can now build biologically accurate brain models of bigger and bigger brain regions and at a higher and higher resolution, further advancing the case for simulation."

Henry Markram PhD, Project, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.

In connectomics, the study of the network structure of connected neurons, great advances are being made on two different scales: that of macro- and meso-scale connectomics, studying the connectivity between populations of neurons, and that of micro-scale connectomics, studying connectivity between individual neurons. We combine these two complementary views of connectomics to build a first draft statistical model of the micro-connectome of a whole mouse neocortex based on available data on region-to-region connectivity and individual whole-brain axon reconstructions. This process reveals a targeting principle that allows us to predict the innervation logic of individual axons from meso-scale data. The resulting connectome recreates biological trends of targeting on all scales and predicts that an established principle of scale invariant topological organization of connectivity can be extended down to the level of individual neurons. It can serve as a powerful null model and as a substrate for whole-brain simulations.

Michael W. Reimann, Michael Gevaert, Ying Shi, Huanxiang Lu, Henry Markram and Eilif Muller.

The authors thank Lida Kanari for help with the validation of projection types, Joseph Knox for assistance with the projection from the Allen common coordinate framework into a 2d plane, and Dimitri Rodarie & Max Nolte for feedback on the paper. This study was supported by general funding to the Blue Brain Project from the Swiss government’s ETH Board of the Swiss Federal Institutes of Technology and by support to BBP as one of its research centers by the École polytechnique fédérale de Lausanne.

The authors declare no competing interests.

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Sep 12 2019   Fetal Timeline   Maternal Timeline   News  

Rendering of mouse neocortex connections by the Blue Brain Project.
CREDIT Blue Brain Project/EPFL.

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