Richard Zare and his colleagues have taken the first step in the complex journey of understanding how humans think: They've developed a way to decipher the chemical signals that are relayed between neurons.
This method uses lasers to trap the smallest of brain cells and analyze their contents to read what Zare calls "thought packets." In unlocking this small pouch of chemicals, the Stanford University chemistry professor believes researchers will now have access to the source of almost all of the communications that take place in the brain. But for the moment, the technique is helping Zare realize how much there is to know about the brain.
"Many people believe the brain is a giant chemical machine, but we don't know what the chemicals are," said Zare, who is the leader of the research team. "People do things like taking slices of the brain and saying it's made of this or that matter, but that's crude. It would be like breaking a computer open, taking out the board, and saying the computer is made entirely of silicon."
The work Zare and his team plan to do with this new technique goes beyond breaking down the brain into its cortical regions or sorting out chemicals like serotonin. They want to know more than the mere fact that serotonin levels affect whether a person suffers from depression, for instance. The delicate chemical balance of the brain creates certain subtleties that scientists will now have a chance to study.
"The question is: Does a cell put out just serotonin or something else that modifies the seratonin at the synapse?" said Zare.
To get at these subtleties, researchers have to get at the contents of vesicles, the tiny cells in the brain that carry chemical messages between neurons. These messages govern a variety of bodily functions and processes ranging from reproduction to pain reaction. These cells are so small that more than a billion of them could fit into a drop of water.
It is because vesicles are so small in humans that Zare and his team have been working on the brains of sea slugs where these cells are roughly a thousand times larger. By working on the larger vesicles, the researchers can test their techniques and then fine-tune them for smaller human vesicles.
To get the vesicle, the researchers used a laser to trap the cell in solution. The vesicle moved along to the most intense part of the laser's beam and stopped. "It's like taking a pair of tweezers and holding it in place -- only the tweezers are a laser," explained Zare.
The researchers used this first laser to move the vesicle to the opening of a capillary, a tube of glass tapered to the size of the cell. Next, the scientists simulated what happens to the vesicle when it reaches the synapse -- they broke it open to release the liquid chemical contents.
Then, the researchers added new chemicals to the neurological cocktail to give the existing compounds florescent tags. Once tagged, the vesicle's chemicals are exposed to an electrical field which breaks them down into their molecular components.
These molecules have different masses, charges and shapes, which cause them to move through their liquid surroundings at different rates inside the glass tube. A second laser picks up the tagged molecules, noting their different rates of movement. The resulting data paints a complete picture of the contents of the vesicle.
Zare and his team analyzed several vesicles -- all of which came from the gland that governed egg laying in the sea slug -- and found that the contents of one vesicle can differ greatly from another. In the brain, a single vesicle can stimulate a cell, and each vesicle can send a slightly different stimulus. What this discovery means is a mystery Zare hopes researchers can unravel with the aid of this new technique.
