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Building a digital BRAIN: Scientists create a 'slice' of neocortex tissue with 31,000 neurons and 40 MILLION firing synapses

The digital reconstruction is the latest step in the Blue Brain Project
It contains 31,000 neurons, 55 layers of cells and 207 neuron subtypes
The team has been using supercomputers to simulate neuron behaviour
Its reconstruction has already been used to identified that brain 'states' can be altered simply by adding calcium ions

Published: 11:11 EST, 8 October 2015 | Updated: 03:36 EST, 12 October 2015

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If you want to learn how something works it helps to take it apart and put it back together again.

For 10 years, neuroscientists have used this strategy on the brain of a rat to learn more about its neurons and synapses, and the result is the first digital reconstruction of brain tissue ever made.

This reconstruction contains 31,000 neurons, 55 layers of cells and 207 different neuron subtypes each mapped and connected in way that mimics exactly how the rat's brain works.

For 10 years, neuroscientists have studied the brain of a rat to learn more about its neurons and synapses. The result is the first digital reconstruction of brain tissue (pictured) ever made that contains 31,000 neurons, 55 layers of cells and 207 different neuron subtypes each mapped and connected accurately

It is the latest step in the Blue Brain Project at the Ecole Polytechnique Federale de Lausanne (EPFL) in Switzerland.

Director of the project, Professor Henry Markam said: In the first 10 years we mainly focused on reverse engineering the neocortical tissue, where we looked at the cell densities, we looked at the number of cell types that there are, the morphology of cells and the kind of connections they form.

'In the second 10 years we focused on developing algorithms and software that would allow us to take the sparse data and constrain it in a digital reconstruction.'

The reconstruction began by placing the neurons in a 3D model. The exact placement of these neurons was plotted using an algorithm that had been trained using the brain of the juvenile rat.

The next step was to connect those neurons.

'For that, first we had to find out where those neurons were touching each other,' explained project scientist Dr Michael Reimann.

The reconstruction (pictured left and right) began by placing the neurons in a 3D model. The exact placement of these neurons was plotted using an algorithm that had been trained using the brain activity of the juvenile rat

The next step was to connect those neurons. Firstly, they had to discover which neurons were touching each other before 'pruning' these connections to show only those which provide connectivity (illustrated). The 'brain slice' is based on the neocortex and includes nearly 40 million synapses and 2,000 connections

Each of those touches was a potential location for a synapse so the researchers had to 'prune' the synapses to show only those which provided connectivity.

Fellow project scientist, Professor Idan Segev added: 'From this you get "music" from electrical activity that should imitate the real biological network that you're trying to understand.'

MAKING BRAINS TRANSPARENT

Last month, researchers at the Riken Brain Science Institute in Japan developed a technique for turning brain tissue transparent to make it easier to study and illuminate the 3D brain's anatomy.

Known as 'optical clearing', it involves making human tissue transparent in order to view even the most detailed and complex processes with advance miscroscopy.

Previous 'clearing' techniques have damaged the cells, but the Japanese researchers not only created a safer method, they also developed 'see-through' samples to study what happens in the brains of Alzheimer's sufferers.

In recent years, generating see-through tissue has become a goal for many researchers in life sciences because of its potential to reveal complex structural details of our bodies, organs, and cells.

This is especially useful when combined with advanced microscopy imaging techniques, but previous methods were limited because the transparency process itself can damage the structures being studied.

The 'brain slice' is based on the neocortex - an area of the brain that has been extensively studied and includes nearly 40 million synapses and 2,000 connections between each brain cell type.

Once the reconstruction was complete, the team used supercomputers to simulate the behaviour of neurons under different conditions.

The researchers found that, by slightly adjusting just one parameter such as the level of calcium ions, they could change the patterns of circuit-level activity.

Many of these changes would not have been identified simply by studying the features of individual neurons.

For instance, slow synchronous waves of neuronal activity, which have been observed in the brain during sleep, were triggered in the researchers' simulations.

This suggests that neural circuits may be able to switch into different 'states', and these could determine certain behaviours.

'An analogy would be a computer processer that can reconfigure to focus on certain tasks,' said Professor Markram.

'The experiments suggest the existence of a spectrum of states, so this raises new types of questions, such as 'what if you're stuck in the wrong state?''

For instance, Markram suggested that the findings may open up new way to study the fight-or-flight response.

The research is published in the journal Cell and all of the results of the Blue Brain Project are available online.

Last month, researchers at the Riken Brain Science Institute in Japan developed a technique for making brain tissue transparent to make it easier to study and illuminate the 3D brain's anatomy.

Last month, researchers at the Riken Brain Science Institute in Japan developed a technique for making brain tissue transparent (pictured). Known as 'optical clearing', the technique is useful because it makes viewing detailed and complex processes with advance miscroscopy easier

After showing how ScaleS treatment can preserve tissue, the researchers put the technique to practical use by visualising the mysterious 'diffuse' plaques seen in the postmortem brains of Alzheimer's disease patients in 3D (pictured). These are typically undetectable using 2D imaging

Known as 'optical clearing', it involves making human tissue transparent in order to view even the most detailed and complex processes with advance miscroscopy.

The original 'recipe' reported by the Dr Miyawaki team in 2011 - called Scale - was an aqueous solution based on urea that suffered from this problem.

The research team spent the past four years improving the effectiveness of the original recipe to overcome this critical challenge, and the result is called ScaleS.

'The key ingredient of our new formula is sorbitol, a common sugar alcohol,' revealed Miyawaki.

'By combining sorbitol in the right proportion with urea, we could create transparent brains with minimal tissue damage, that can handle labelling techniques, and is even effective in older animals.'

This new technique creates transparent brain samples that can be stored in the solution for more than a year without damage.

After showing how ScaleS treatment can preserve tissue, the researchers also put the technique to practical use by visualising the mysterious 'diffuse' plaques seen in the postmortem brains of Alzheimer's disease patients in 3D.

These are typically undetectable using 2D imaging.