Digital piece of rat brain reconstructed in a super computer by scientists

The best way to find out how something works is to take it apart and then try to put it all back together again. This is something researchers claim to have done with a slice of juvenile rat brain.

The scientists explained in the journal Cell (citation below) how they completed the first draft of this reconstruction, which contains more than 31,000 neurons, fifty-five layers of cells, and 207 different neuron subtypes.

In what the scientific community describes as ‘heroic efforts’, researchers are trying to define all the different kinds of neurons in the brain, as well as measuring their electrical firing properties, and mapping out the circuits that interconnect them.

This is a photo of a virtual brain slice. (Credit: Makram et al./Cell 2015)

Their research is starting to give us a glimpse into the building blocks and logic of how the brain is wired.

However, it is no easy feat to get a full, high-resolution picture of all the features and activity of the neurons inside a brain region.

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Rat brain part of the Blue Brain Project

Prof. Henry Markram, who is working on the Blue Brain Project at EPFL (École polytechnique fédérale de Lausanne) in Switzerland, and team have taken an engineering approach to this question. They have digitally reconstructed a slice of the neocortex of a young rat.

The neocortex is a part of the cerebral cortex in the brain concerned with hearing and sight in mammals. It is regarded as the most recently evolved part of the cortex.

The Blue Brain Project is an attempt to reverse engineer the human brain and reconstruct it at the cellular level inside a computer simulation.

The researchers built a virtual (rat) brain slice representing the different types of neurons present in this region of the brain, and the key features controlling their firing. They also modelled the neurons’ connectivity, including almost 40 million synapses and 2,000 connections between each brain cell type.

Prof Henry Markram.

Prof. Markram said:

“The reconstruction required an enormous number of experiments. It paves the way for predicting the location, numbers, and even the amount of ion currents flowing through all 40 million synapses.”

After completing the reconstruction, the team used powerful supercomputers to simulate neuron behavior under different conditions.

They were amazed to find that by slightly adjusting one parameter – calcium ion levels – they were able to produce broader patterns of circuit-level activity that could not be predicted based on individual neuron features.

Neural circuits can shift from ‘state’ to ‘state‘

For example, slow synchronous waves of neuronal activity, which have been detected in the brain during sleep, were triggered in their simulations. This suggests that neural circuits can probably switch into different ‘states’ that could underlie important behaviors.

Prof. Markram said:

“An analogy would be a computer processer that can reconfigure to focus on certain tasks. 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 example the team suggests that their findings may help explain how initiating the fight-or-flight response through the adrenocorticotropic hormone yields aggression and tunnel vision.

The Blue Brain Project scientists say they plan to carry on exploring the state-dependent computational theory while improving the model they have constructed. Their results so far are freely available here.

Citation:

“Reconstruction and Simulation of Neocortical Microcircuitry,” Markram, Henry et al. Cell , Volume 163 , Issue 2 , 456 – 492.

Video – Reconstruction and Simulation of Neocortical Microcircuitry