A large international team of researchers from the Blue Brain Project has digitally reconstructed and simulated a slice of a juvenile rat’s neocortex, an area of the brain unique to mammals that composes the top-most layer of the cerebral cortex.
Simulation of electrical activity in a virtual brain slice formed from seven unitary digital reconstructions of neocortical microcircuits. Image credit: BBP / EPFL.
The team, led by Dr Henry Markram of the Ecole Polytechnique Federale de Lausanne, Switzerland, created a detailed computer representation of about a third of a cubic millimeter of brain tissue containing about 30,000 neurons connected by nearly 40 million synapses.
The scientists performed tens of thousands of experiments on neurons and synapses in the neocortex of young rats and catalogued each type of neuron and each type of synapse they found.
They identified a series of fundamental rules describing how the neurons are arranged in the neocortical microcircuit and how they are connected via synapses.
“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,” said Dr Markram, who is a co-lead author of a paper published in the journal Cell.
Once the reconstruction was complete, the team used powerful supercomputers to simulate the behavior of neurons under different conditions.
Remarkably, the scientists found that, by slightly adjusting just one parameter, the level of calcium ions, they could produce broader patterns of circuit-level activity that could not be predicted based on features of the individual neurons.
For instance, slow synchronous waves of neuronal activity, which have been observed in the brain during sleep, were triggered in their simulations, suggesting that neural circuits may be able to switch into different ‘states’ that could underlie important behaviors.
“When we decreased the calcium levels to match those found in awake animals and introduced the effect that this has on the synapses, the circuit behaved asynchronously, like neural circuits in awake animals,” said co-lead author Dr Eilif Muller, also of the Ecole Polytechnique Federale de Lausanne.
“An analogy would be a computer processor 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,” Dr Markram added.
The findings may open up new avenues for explaining how initiating the fight-or-flight response through the adrenocorticotropic hormone yields tunnel vision and aggression.
“The reconstruction is a first draft, it is not complete and it is not yet a perfect digital replica of the biological tissue,” Dr Markram said.
“In fact, the current version explicitly leaves out many important aspects of the brain, such as glia, blood vessels, gap-junctions, plasticity, and neuromodulation.”
“The job of reconstructing and simulating the brain is a large-scale collaborative one, and the work has only just begun,” concluded co-senior author Dr Sean Hill, also of the Ecole Polytechnique Federale de Lausanne.
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Henry Markram et al. 2015. Reconstruction and Simulation of Neocortical Microcircuitry. Cell, vol. 163, no. 2, p. 456-492; doi: 10.1016/j.cell.2015.09.029
