Communications of the ACM
Scientists Create First Realistic 3-D Reconstruction of Brain Circuit
Researchers from the lab of Nobel laureate Bert Sakmann, MD, at the Max Planck Florida Institute are reporting that, using a conceptually new approach and state-of-the-art research tools, they have created the first realistic three-dimensional diagram of a thalamocortical column in the rodent brain. A vertically organized series of connected neurons that form a brain circuit, the cortical column is considered the elementary building block of the cortex, the part of the brain that is responsible for many of its higher functions.
This achievement is the first step toward creating a complete computer model of the brain, and may ultimately lead to an understanding of how the brain computes and how it goes awry in neurological, neurodevelopmental and psychiatric disorders. The study, "Cell Type–Specific Three-Dimensional Structure of Thalamocortical Circuits in a Column of Rat Vibrissal Cortex," by Marcel Oberlaender, Christiaan P. J. de Kock, Randy M. Bruno, Alejandro Ramirez, Hanno S. Meyer, Vincent J. Dercksen, Moritz Helmstaedter, and Bert Sakmann, is published online in the journal Cerebral Cortex.
"This is the first complete 3-D reconstruction of a realistic model of a cortical column," says Marcel Oberlaender, first author on the paper. "This is the first time that we have been able to relate the structure and function of individual neurons in a live, awake animal, using complete 3-D reconstructions of axons and dendrites. By creating this model, we hope to begin understanding how the brain processes sensory information and how this leads to specific behaviors."
The electrically excitable axon extends from the body of the neuron (brain cell) and often gives rise to many smaller branches before ending at nerve terminals. Dendrites extend from the neuron cell body and receive messages from other neurons.
In addition to recreating the structure of the cortical column, the study also sheds significant light on the function of its constituent neurons, and the relationship between their functionality and structure. In looking at neurons' response to sensory stimulation, the researchers discovered that sensory-evoked activity in some of the cells can be directly correlated with their structure and connectivity, which marks a first step toward understanding basic organizational principles of the brain.
Working with both awake and anesthetized rats, and also examining stained brain slices, the neuroscientists used sophisticated new light microscopy as well as custom designed tools to examine 15,000 neurons of nine identified cell types. Using a painstaking, six-step process, the researchers identified and reconstructed the column's constituent parts using sophisticated software and a range of other new state-of-the-art tools and processes.
Described in a related paper co-authored by Drs. Sakmann and Oberlaender, these new methods, which were developed in part at the Max Planck Florida Institute, allow researchers, for the first time, to simulate electrical signaling in a computer model at subcellular and millisecond resolution.
"We can now quantify the number of neurons of each cell type, their three-dimensional structure, connectivity within these networks, and response to sensory stimulation, in both an anesthetized and awake animal," Oberlaender says. "Such a quantitative assessment of cortical structure and function is unprecedented and marks a milestone for future studies on mechanistic principles that may underlie signal flow in the brain, during such functions as decision making"
Oberlaender is part of the Max Planck Florida Institute's Digital Neuroanatomy group, led by Sakmann. The group focuses on the functional anatomy of circuits in the cerebral cortex that form the basis of simple behaviors (e.g. decision making). One of the group's most significant efforts is a program dedicated to obtaining a three-dimensional map of the rodent brain. This work will provide insight into the functional architecture of entire cortical areas, and will lay the foundation for future studies on degenerative brain diseases, such as Alzheimer's.
Oberlaender and Christiaan de Kock contributed equally to this work. De Kock is with the Neuroscience Campus Amsterdam, VU University Amsterdam, the Netherlands. The research team also included scientists from Max Planck Institute for Medical Research (Heidelberg, Germany), Columbia University and Zuse Institute (Berlin).
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