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 the brain’s neuronal network, including the identification of more than 18,000 separate neurons within cortical columns 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.
This highly accurate analysis provides a functional and anatomical blueprint of the exact dimensions, the number and types of neurons involved, and their distribution within a standard cortical column. 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 in animal brains to help us understand how the brain works,” said Hanno S. 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 as the sensory system 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 importance of the columns, this groundbreaking research provides the first 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.
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.
“Frankly,” Meyer said, “knowing the exact number of neurons and their distribution has become even more important if you want to create computer generated models.”
To quantify how the various signals are distributed between the thalamus and the somatosensory cortex, the scientists labeled the neurons with fluorescent markers, which could be viewed by advanced microscopy techniques.
Locating the individual neurons, however, was basically done by hand.
“We manually counted the neurons in three entire whisker columns over the course of two years,” Meyer said. “As a result, we generated terabytes of imaging data of these sections of the brain. 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, including a precise estimation of the potential output of a standard cortical column – an estimated 4441 signals within 100 milliseconds of a whisker twitch.
“By combining functional data and our new anatomical findings we can predict the input and output signals in one of the cortical columns when you touch a whisker,” Meyer said. “This accuracy 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.
“We want to count the rest of the columns in the sensory cortex,” Meyer said, “then we’ll move onto the brains of mice with Alzheimer’s to see what might go wrong in the early stages of the disease.”
As for mapping the entire brain, it’s still a ways off but getting closer.
“The mapping project is so massive that we may have to start thinking about doing it on a very large scale, much like they did with the human genome,” he said.
The Digital Neuroanatomy group at the Max Planck Florida Institute is headed by Bert Sakmann, MD, Ph.D. who, along with physicist Erwin Neher, was awarded the 1991 Nobel Prize in Medicine. The group focuses on studying the functional anatomy of circuits in the brain – specifically the cerebral cortex – that form the basis of simple behaviors such as decision making. This research involves the use of large scale, high resolution microscopy techniques to reconstruct individual structures, locations and the synaptic wiring of different neuron types. Eventually, this may reveal parts of the network that trigger sensory initiated behavior and lead to new discoveries about the brain’s process of learning.
Verena C. Wimmer, Randy M. Bruno, Christiaan P.J. de Kock, Thomas Kuner, and Bert Sakmann
Dimensions of a Projection Column and Architecture of VPM and POm Axons in Rat Vibrissal Cortex
Cereb. Cortex (2010) 20(10): 2265-2276 first published online May 7, 2010 doi:10.1093/cercor/bhq068
Hanno S. Meyer, Verena C. Wimmer, M. Oberlaender, Christiaan P.J. de Kock, Bert Sakmann and Moritz Helmstaedter
Number and Laminar Distribution of Neurons in a Thalamocortical Projection Column of Rat Vibrissal Cortex
Cereb. Cortex (2010) 20(10): 2277-2286 first published online June 9, 2010 doi:10.1093/cercor/bhq067
Hanno S. Meyer, Verena C. Wimmer, Mike Hemberger, Randy M. Bruno, Christiaan P.J. de Kock, Andreas Frick,Bert Sakmann and Moritz Helmstaedter
Cell Type–Specific Thalamic Innervation in a Column of Rat Vibrissal Cortex
Cereb. Cortex (2010) 20(10): 2287-2303 first published online June 9, 2010 doi:10.1093/cercor/bhq069
About the Max Planck Florida Institute:
The Max Planck Florida Institute (MPFI), part of the prestigious Max Planck Society based in Germany, seeks to provide new insight into important biological questions using innovative experimental and theoretical methodologies. With a focus on the organization and function of cellular assemblies in the brain and other complex tissues, research at the MPFI aims to provide a quantitative understanding of biological systems employing expertise and technologies from neuroscience, cell biology, genetics, the physical sciences, and engineering. By embracing a wide vision of biology from nanotechnology to cellular structure to novel model organisms, research at the MPFI aims to unlock bottleneck questions in our understanding of the biological world and the advancement of human health. The Max Planck Florida Institute broke ground on their new 100,000-square-foot biomedical facility last June. The permanent biomedical research center and laboratories are expected to be completed by early 2012. For more information, visit www.maxplanckflorida.org.