With its 100 billion neurons (brain cells) and its 100 trillion synapses, the human brain is a complex multi-level system. The connections among the neurons form a hierarchy of circuits, from local microcircuitry up to the level of the whole brain. Meanwhile at a lower level, every neuron and every synapse is a complex molecular machine in its own right. It is the interactions between these levels, which give rise to human behaviour, human emotion and human cognition.
The EPFL Blue Brain Project aims to build comprehensive digital reconstructions (computer models) of the brain, which include the brain’s different levels of organization and their interactions, and which are compatible with the available experimental data.
The BBP’s reconstruction strategy identifies interdependencies in the experimental data (e.g. dependencies between the size of neurons and neuron densities, dependencies between the shapes of neurons and the synapses they form, dependencies between the numbers of “boutons” on axons and synapse numbers) and uses them to “constrain” the reconstruction process. Multiple, intersecting constraints allow the project to build the most faithful reconstructions possible from the sparse available experimental data– avoiding the need to “measure everything”. In fact, the BBP’s latest reconstruction of the cortical microcircuit connectivity is based on experimental data representing less than 1% of the synaptic connections in the circuit. Lab experiments providing new data and constraints make it possible to test and progressively improve the digital reconstruction.
In 2015, Blue Brain reached a major milestone with the publication of a first draft of the digital reconstruction of neocortical microcircuitry (Markram et al, 2015). The study confirmed the feasibility of building and simulating a digital copy of a part of the brain and demonstrated that multidisciplinary Big Science in the field of neuroscience yields favorable results (82 scientists contributed to the study).
The paper, which appeared in the journal Cell, represents the most complete description of any neural microcircuit to date. It provides a complete digital map of all the cells and synapses in a block of neural tissue and describes simulation experiments replicating a range of previous in vivo experiments. In other words, Blue Brain’s digital copy of a part of the brain behaves like a real part of the brain.
Most significantly, this study advances the case for simulation as a useful new method in neuroscience. It proves that we understand the basic properties of the components and interconnections of the brain well enough to be able to reconstruct and simulate certain physiological functions. This advance makes it feasible, in principle, to reconstruct the human brain even though we can never measure all its parts.
Consequently, Blue Brain has now:
- Built a digital copy of the whole somatosensory cortex with around four million neurons, a part of the hippocampus (a brain region that serves as our GPS system in the brain) and a microcircuit of the thalamus (a part of the brain that organizes all the information that goes to and from the neocortex)
- Produced the first draft model of the rules guiding neuron-to-neuron connectivity of a whole mouse neocortex. Based on these rules, the team has generated statistical instances of the micro-connectome of 10 million neurons, a model spanning five orders of magnitude and containing 88 billion synaptic connections that will serve as the basis of the world’s largest-scale simulations of detailed neural circuits.
- Released the Blue Brain Cell Atlas – the first digital 3D atlas of every cell in the mouse brain. This provides neuroscientists with previously unavailable information on major cell types, numbers and positions in all 737 brain regions.
- Mapped the kinetic behavior of the largest family of ion channels: Kv channels and provided open access to the million-plus Kv channel recordings from over 18,000 cells, and a growing dataset for other channels. These are publicly available for download on the dedicated, wiki-like platform Channelpedia. channelpedia.epfl.ch
- Helped other groups to build digital copies of the cerebellum and the basal ganglia.
Data and neuron models used in our current reconstructions are available on the Blue Brain Portal – a knowledge space for simulation neuroscience.