Synapse Microarray Will Hold Neurons in Place

Treating Alzheimer’s with drugs that enhance synaptic strength

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This segment is part of the IEEE Spectrum series “The New Medicine

Susan Hassler: Here’s a question for you: What do Facebook and neuroscience have in common? Give up? It’s a belief that you are your connections. Samuel K. Moore went to MIT, in Cambridge, Massachusetts, to report on the latest research on Alzheimer’s disease.

Samuel K. Moore: Neuroscience has shown more and more dramatically that how the cells in your brain connect to each other is the secret to what we think, feel, and do—and how we remember what we thought, felt, and did. Unfortunately, it’s also finding that when those connections are interrupted...disease results. Those connections—from one neuron to another—are called synapses, and they’re crucial to information processing in the brain.

Mehmet Fatih Yanik: Many neurodegenerative diseases—like Alzheimer’s, for instance—are basically either effecting synapses or are caused by malfunctioning synapses. So a lot of pharmaceutical companies today are interested in finding drugs that can enhance synaptic strength and modulate it.

Samuel K. Moore: That’s Mehmet Fatih Yanik, a professor of biomedical engineering at MIT. He and his students have built a device that could help find drugs to enhance and modulate synaptic strength a whole lot quicker—possibly compressing years of searching into just a few months.

Samuel K. Moore: The device is called a synapse microarray. Using high-powered lasers and some of the same techniques Intel uses to make microchips, Yanik and his students built microscopic structures designed to hold neurons in place. Each neuron, when placed on the chip, is forced to grow a projection, called an axon, through a microscopic channel.

Samuel K. Moore: The channel leads to a chamber holding a target cell. Will the neuron connect with its target?

Samuel K. Moore: Will the connection be strong...or weak?

Samuel K. Moore: A strong or weak connection is determined by the chemicals with which you surround the synapse. Yanik’s microarrays let you try out a lot of different chemicals in a short amount of time.

Mehmet Fatih Yanik: A machine can go and measure the synaptic strength much faster and much more reliably than any existing technology.

Samuel K. Moore: Yanik says they can measure synaptic strength 10- to 100-fold faster.

Mehmet Fatih Yanik: This makes this technology much faster in terms of screening large chemical libraries looking for specific chemicals that can enhance synapses.

Samuel K. Moore: These chemical libraries can be quite large, containing a million or even 3 million chemicals. So speed is very important. Let’s say [you] want to screen a medium-size of library of 100 000 chemicals. That would take several years, using the technologies pharmaceutical companies use today.

Mehmet Fatih Yanik: This is too long of a time frame, because you have to do so many other things to develop a drug. You cannot spend a few years trying to hunt for the lead chemicals. With our technology, we can do the same screen in just a matter of a few months.

Samuel K. Moore: Finding a chemical that can alter the strength of neural connections could be key to fighting or at least slowing down diseases like Alzheimer’s. In neurodegenerative diseases like Alzheimer’s, the brain is constantly losing neurons—constantly losing connections.

Mehmet Fatih Yanik: The capability to enhance the processing power of the intact brain by inducing neurons to make more synapses can actually compensate for the functional decline in Alzheimer’s.

Samuel K. Moore: He might know the needs of doctors and drug developers well, but Yanik isn’t either. He’s not even a neuroscientist. He’s a laser guy. He spent the early part of the decade working on one of the hottest physics discoveries of its time—slowing down and even stopping the fastest thing in the universe, light.

[whistle with pitch decreasing to nearly 0 hertz]

Mehmet Fatih Yanik: After a while, I got bored with what I was doing at the time.

Samuel K. Moore: Sorry—you got bored with stopping light?

Mehmet Fatih Yanik: Yes. You could say that.

Samuel K. Moore: So Yanik trained his lasers on the maladies of the brain. His first work put a new tool in the hands of scientists trying to figure out how brains reestablish connections after injury. Working with neuroscientists at Stanford University, he turned one of the most extreme lasers available into a scalpel so precise that it could cut the connection between two neurons without damaging anything else.

The laser is called a femtosecond laser, because it fires pulses of energy that last for a few tens of femtoseconds. What’s a femtosecond? Glad you asked. Here’s Mark Scott, a Ph.D. candidate in Yanik’s lab.

Mark Scott: My favorite way to describe this is if you think of a jet fighter on afterburner, it will move less distance than [a] hydrogen atom in the time that a femtosecond passes. So, this laser has a pulse length of about 100 femtoseconds. So I think that it moves a few hydrogen atoms in that time.

Samuel K. Moore: Now they’re using that laser to help build better synapse microarrays. The brain has a very highly organized architecture, so it can fail at the level of cells or at a higher level—the level of circuits.

Yanik’s lab is at work building much more complex arrays that contain neural circuits which are able to simulate simple processes we know go on in our own brain, such as memory and feedback. They’ll use the circuits to test new drugs. And with these better arrays, they hope, will come better treatments. I’m Samuel K. Moore.

Photo: Christine Daniloff/MIT