Thursday, November 06, 2008

Connectomics - Tracing the Wires of the Brain

A cool article on the brain from the Dana Foundation. It's fascinating to watch the explosion in knowledge about the brain. We are at a time comparable to the great explorers when it comes to brain research. It'll be decades, I think, before anyone really begins to understand what they are looking at, but that's cool, too.


Tracing the Wires of the Brain

By Sebastian Seung, Ph.D.
About Sebastian Seung, Ph.D.
November 03, 2008

Scientists working with rapidly advancing computer technology and electron microscopes hope one day to map the billions of neuronal connections in the brain. The resulting map, or “connectome,” could help us understand memory, intelligence and mental disorders, Dr. Sebastian Seung writes.

Suppose that someone gave you a radio and asked you to figure out how it works. You could try measuring electrical signals inside it, but the measurements might not be sufficient. You might be more successful if you were also given a circuit diagram illustrating all the components of the radio and how they are connected to each other.

Now imagine that your goal is to discover how a brain works. A map of brain connections would be helpful for interpreting measurements of the signals transmitted between neurons. In the human brain, these signals travel in a complex network of 100 billion or so neurons, each of which is connected to 10,000 others.

Such a map of a brain, human or otherwise, does not yet exist. But as technology advances, researchers are setting their sights on the “connectome,” a word coined in a 2005 study by Olaf Sporns and colleagues to describe a complete map of connections in a brain or a piece of a brain.

Genome and Connectome

“Connectome” was coined in analogy with the “genome”—the entirety of an organism’s hereditary information—studied by biologists. To imagine how the story of the connectome will unfold over the next few decades, it’s helpful to recall the history of the genome.

In 1953 James Watson and Francis Crick proposed the double helix structure for DNA. The double helix consists of a long chain of repeated units called nucleotides, of which there are four types: A, C, G, and T. Hereditary information is written in DNA using this alphabet of four letters. In the human genome, the sequence of nucleotides is about one billion letters long. The reading of this sequence was finally completed by the Human Genome Project in 2003.

The story of the connectome began when scientists first realized that the brain comprises a network of neurons. This happened around 1900, well before the double helix of Watson and Crick. But the connectome story is still in the future, and I believe the discoveries that compose this saga will be among the great prizes of 21st-century neuroscience.

Revealing connectomes will be much more difficult than identifying genomes. But I and others are now optimistic that the connectome will eventually be transformed from dream into reality. A new field of neuroscience will be created: “connectomics.” This new field will be driven by new technologies, as we will see. It will take shape alongside other research approaches, and these multiple methods will provide better insight into the brain’s complex structure than any individual method can.

Three-Dimensional Nanoscale Imaging

Connectomics is more challenging than genomics; the structure of the brain is extraordinarily complex. You have probably seen images of neurons before. A single neuron has a fantastic shape, forking out many branches to form a tree-like structure. But if you have only seen pictures of neurons in isolation, you may not fully appreciate the complexity of brain structure.

Before researchers study a single neuron under a microscope, they inject it with a stain. The neurons around it remain invisible because without the stain they are transparent. This technique is valuable for seeing the shape of a single neuron clearly. However, it does not give an accurate impression of what the brain is really like, because neurons are not islands in the brain. Instead, their forking branches are tightly entangled with each other. The brain can be compared to a giant bowl of spaghetti, in which each strand has been replaced by a complex, branched noodle.

Because their branches are so tightly entangled, neurons are locked in a multi-way embrace. At a point of contact between a pair of neurons, they can form a synapse, a junction at which one neuron sends chemical messages to another. When a synapse exists, the pair of neurons is said to be “connected.” The term should not be taken too literally, as there is still a narrow gap separating the two neurons, and the molecules in chemical messages have to float across this gap. The term is used in the metaphorical sense of communication, just as two people talking on cell phones are said to be connected. The efficacy of communication between a pair of connected neurons is known as the “strength” of the connection. If two neurons are strongly connected, the messages between them come in loud and clear, but if they are weakly connected, the messages are faint. Entanglement increases contact points between neurons, providing more potential locations for synapses, which allow neurons to communicate, or be “connected.”

Although entanglement is a crucial aspect of brain structure, it’s impossible to see with an ordinary light microscope. According to the laws of physics, structures smaller than the wavelength of light cannot be seen clearly using such a microscope.* The thinnest branches of neurons are less than a tenth of a micron in diameter, which is less than the wavelength of visible light. Luckily, another kind of microscope uses electrons rather than light, and yields images with much higher spatial resolution. With an electron microscope, the branches of neurons can be seen clearly, even when they are tightly packed together in the brain.

By itself, a microscope cannot be used to see the interior of the brain, which is essential for observing brain structure. So, to see every location in the brain, scientists slice brain tissue into thin sections with a knife. By the combined use of the knife and the microscope, a sequence of two-dimensional images is acquired. Together these images show the entire three-dimensional brain structure.

Read the whole article.

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