Today, I’ll discuss an article, published early this month in Cell (october 8). The authors present a first-draft digital reconstruction of the microcircuitry of somatosensory cortex of juvenile rat, actually a neocortical volume of 0.3 mm3 (about the size of a grain of sand) containing ∼31,000 neurons, connected at almost ∼37 million synapses.

These are the first results of a collaboration between different labs and between scientists, informaticians, physicists and engineers:  the Blue Brain Project. Headed by Henry Markram from the Brain and Mind Institute of the École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland, it aims at creating a synthetic brain by reverse-engineering mammalian brain circuitry. Started 20 years ago, it fostered a lot of criticism among the scientifical communauty, which reached its climax in 2014 when, on 7 July,  an open letter was sent to the European Commission by 154 European researchers threatening to boycott the project. They pointed out the significant risk that this simultaneously narrow and ambitious approach will fail to meet its goals. Central to this controversy was funding : the Blue Brain Project and its descendant, the Human Brain Project launched in 2013, is funded by the European Commission and will receive up to one billion euro over ten years.

Here is the video published by Cell, in which the authors explain their work and results:

A plateform for in silico neuroscience

The first years hab been devoted to reverse engineering the neurocortical tissue. Different parameters had been determined: cell densities, number of cell types, morphologies of cells, way they are connected (anatomy, physiology, electrophysionomy of neurons). 3D reconstruction, placement of axons and dendrites, and the reconstruction of the morphology of cells enabled to build a digital network consistent with neurocortical architecture. In the second ten years, they focused on developing algorithms, softwares and an ecosystem which would allow to take these diverse data and constrain them in a dense reconsruction of the neurocortical tissue. To connect those neurons, they prone the touches to match key experimental constraints according to principles of synaptic connectivity. The electric characterisation of 11 cell types enabled to determine their firing pattern. They then combined the things together to get a idea of the electrical activity of these network of neurons which should imitate the real biological physiology of the cortical network.

According to Henry Markram, even if you can’t mesure everything experimentally, the sparse data that are obtained provide sufficient constraints to give a first approximation of the microcircuity. For the authors, this reconstruction is a scaffold. They strive to add the missing biological data (intercellular space, glia, blood vessels, molecular pathways inside neurons and synapses) and refine the biological accuracy of the reconstruction by taking feedback from the communauty and regularly releasing a new version of the circuity. They want to make it a plateform for in silico neuroscience. The reconstruction can be accessed online at the portal called The Neocortical Microcircuit Collaboration Portal (https://bbpnmc.epfl.ch/nmc-portal/web/guest/welcome). 

Visualization of spontaneous activity in the in silico slice under depolarization and in vitro calcium conditions ([Ca2+]o = 2.0 mM). Neuronal dendrites are coloured according to the local voltage and a heat colormap.

Will this publication abate the criticism aroused by these big collaborative projects? Only time will tell.
About brain studies, only one thing is certain: a lot is to be done in this unknown and open field… and that is exciting.

Reconstruction and Simulation of Neocortical Microcircuitry. Markram, Muller, Ramaswamy, and Reimann et al. Cell. October 8, 2015.




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