Max Planck scientists create anatomically detailed map of the brain's neuronal networks

New findings will boost computer-driven studies of brain function and pathologies

October 12, 2010

In three closely related studies, scientists from the Max Planck Florida Institute have provided one of the most comprehensive analyses to date of the detailed architecture of a fundamental part of the brain’s neuronal network, the “cortical column” of the cerebral cortex.   The three studies were featured on the cover of the October issue (Volume 20, Issue 10) of the journal Cerebral Cortex, and were the subject of a special commentary in the same issue by two renowned neuroscientists, Edward G. Jones of the University of California and Pasko Rakic of the Yale University School of Medicine.

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All neuronal cell bodies in three complete cortical columns. Cell  bodies from the C2 (blue), D2 (green) and D3 (yellow) column in rat  somatosensory cortex are shown. Neuron somata have been reconstructed in 3D from confocal microscopy data.
All neuronal cell bodies in three complete cortical columns. Cell  bodies from the C2 (blue), D2 (green) and D3 (yellow) column in rat  somatosensory cortex are shown. Neuron somata have been reconstructed in 3D from confocal microscopy data.

This highly accurate analysis provides an anatomical and functional blueprint of the exact dimensions, the number and types of neurons involved, their distribution within a standard cortical column, and the input they receive from the thalamus. Counting and mapping the neuronal networks in the brain is a major unsolved frontier in neuroscience and is an essential step towards understanding how the brain works. The results of the three studies support the creation of sophisticated computer models of the neuronal networks in cortical columns and provide an important piece of the puzzle of mapping the neural networks of the entire brain.

“We are investigating the neuronal networks involved in sensory processing in animal brains to help us understand how the brain works,” said Hanno-Sebastian Meyer, a scientist in the Department of Digital Neuroanatomy at the Max Planck Florida Institute, and the first author of two of the studies, “and we chose the networks in the brain functionally connected to the rodent’s whiskers to do it. With all our data in place, we will ultimately be able to create a computer model of this system, and this is a crucial first step.”

While much of the study of the cerebral cortex has not recognized the full significance of a detailed reconstruction of the columns, this research provides an important quantitative look at these archetypical structures. While done in animal models, the reconstruction published in the articles opens a potential new window on the composition of a significant part of the brain that could lead to a far better understanding of how minor changes in the column structures can cause various sensory and cognitive abnormalities.

Taking a Quantitative Approach

The cerebral cortex, which is central to perception, memory and language, is made up of six layers of nerve cells connected by bundles of neurons in vertical columns that span the cortex itself. The neurons within these cortical columns share similar properties and are considered basic for processing sensory input. The thalamus, a large structure near the center of the brain, acts like a train switching yard, actively relaying signals between the outer senses (seeing, hearing and touch) to the appropriate sensory regions of the cortex via the columns.

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Thalamic input to a cortical column. Synaptic boutons from two thalamic nuclei contacting cortical neurons have been labeled with fluorescent markers (left panel; red: VPM nucleus, green: POm nucleus) and imaged with confocal microscopy. The density distribution of thalamic boutons in a cortical column has been quantified (right panel).
Thalamic input to a cortical column. Synaptic boutons from two thalamic nuclei contacting cortical neurons have been labeled with fluorescent markers (left panel; red: VPM nucleus, green: POm nucleus) and imaged with confocal microscopy. The density distribution of thalamic boutons in a cortical column has been quantified (right panel).

Perhaps the strongest feature of the new studies, the commentary noted, was the quantitative approach taken by the scientists, an approach that involved the careful and painstaking counting of some 17,000 – 19,000 neurons within the vertical columns in what is known as the somatosensory cortex, an area of the brain that processes physical sensations from various parts of the body, in these particular studies, whiskers – with each separate rodent whisker having its own specific cortical column.

Meyer said that they were surprised to find such a large number of neurons in each column since the generally accepted number has been considered closer to 10,000 –half of what they found.

“Clearly,” Meyer said, “knowing the exact number of neurons and their distribution has become even more important if you want to create accurate computer-based models.”

Mapping Neurons

To quantify the number and distribution of all neurons in entire cortical columns, the scientists labeled the neurons with fluorescent markers, which could be viewed by advanced microscopy techniques.

Locating the individual neurons, however, was done by hand, using computer software for visualization and for marking the neurons.

“We manually counted the neurons in three entire whisker columns and the surrounding area over the course of two years,” Meyer said. “During that process, we generated terabytes of imaging data of these sections of the brain and marked more than 100,000 neurons. The manually collected data will provide the basis to design algorithms for automatic counting in the future.”

The results of all this imaging, counting and analysis is a wealth of data on the overall architecture of the cortical columns, and enables the researchers to estimate the potential output of a standard cortical column at a precision higher than ever before – approximately 4400 signals within 100 milliseconds of a whisker twitch.

The studies also involved quantification of the input that different neuron types in a cortical column receive from the thalamus, providing the anatomical basis for the functional measurements at single cell level.

“By combining functional data and our new anatomical findings we can predict and better understand the input and output signals in one of the cortical columns when you touch a whisker,” Meyer said. “The accuracy of our quantitative approach is critical to produce a reliable computer model.”

From this point, Meyer and his colleagues will be moving towards developing the tools to eventually map the entire rodent brain.

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