In 2015, the Blue Brain Project published a landmark paper in Cell: “Reconstruction and Simulation of Neocortical Microcircuitry.” This work, led by Henry Markram, represented the most detailed digital reconstruction of neural tissue ever attempted at that time. It proved that it is possible to build a dense, biologically accurate map of the brain using algorithmic rules derived from sparse experimental data.

The Microcircuit

The team reconstructed a volume of 0.29 mm³ of the juvenile rat somatosensory cortex. While physically small, this “microcircuit” is incredibly dense:

• 31,000 neurons
• 55 morphological types (m-types)
• 207 morpho-electrical types (me-types)
• 8 million connections
• 37 million synapses

Algorithmic Reconstruction: Filling the Gaps

We cannot yet slice a brain and trace every wire for a whole microcircuit. The Blue Brain approach solves this by measuring statistical rules rather than individual wires.

1. Classification: Neurons are cataloged into types (e.g., L5 Martinotti cells, L2/3 Pyramidal cells) based on shape and electrical behavior.
2. Placement: Neurons are positioned in 3D space according to biological density gradients.
3. Connectivity: Synapses are not explicitly traced. Instead, an algorithm connects neurons wherever their axons and dendrites physically touch (Peters’ Rule), refined by pruning rules to match biological connectivity rates.

Emergent Properties

The crucial finding of this study was that emergent properties appeared in the simulation without being explicitly programmed.

• Spontaneous Activity: The network exhibited realistic background firing rates.
• Calcium Dynamics: Changing the simulated calcium concentration shifted the network state from synchronous bursting (sleep-like) to asynchronous activity (awake-like).
• Choristers and Soloists: Some neurons naturally fired in sync with the crowd, while others fired independently, mirroring in vivo observations.

Validation Strategy

The reconstruction was validated against experiments not used to build the model. The team compared the digital synapses to literature data on synaptic conductance, short-term plasticity (facilitation/depression), and connection probability. The match was high, suggesting that if you get the anatomy and the cell types right, the connectivity follows naturally.

Official Sources

• Markram, H., Muller, E., Ramaswamy, S., Reimann, M. W., Abdellah, M., Sanchez, C. A., … & Schürmann, F. (2015). Reconstruction and simulation of neocortical microcircuitry. Cell, 163(2), 456-492.
• The Blue Brain Project
• Neocortical Microcircuit Collaboration Portal