The Neuron Whisperers

(Inside Science) -- Hundreds of billions of neurons tangle together into the two pounds of folded, wrinkly tissue we call the brain. Scientists have spent years trying to eavesdrop on electrochemical signals -- neuronal chatter -- to figure out what happens when a memory is formed or an emotion is felt. Scientists have recently moved beyond implanting electrodes and using functional MRI scans to begin harnessing the power of cell culture and microchips.

They are not only listening to what each neuron is saying, but also starting to talk back.

Growing neurons outside the brain requires two major steps: coaxing the cells to grow on a petri dish and then getting the cells to make connections with each other. Once the neurons have connected, they can "talk" by  sending electrical signals. Researchers, however, have found it difficult to get the neurons to keep talking. Instead of letting the neurons grow haphazardly in cell culture, a group of researchers at the University of Pittsburgh coaxed the growing neurons into a doughnut shape and attached them to a small glass chip. This shape, said first author Ashwin Vishwanathan, let the neurons have a 20 second “conversation” after they were stimulated with a small jolt of electricity. The electrochemical signal circled the doughnut over and over.

The researchers published their results in the journal Lab on a Chip. It might not sound like much, said Vishwanathan, now a postdoc at the Massachusetts Institute of Technology in Cambridge, Mass., but it’s a huge step forward in understanding how memories form.

Short-term memory is how we remember a phone number just long enough to dial it, Vishwanathan said. The formation of these brief memories occurs when neurons show persistent activity, just as they did when in the doughnut shape.

“It’s hard to access the part of the brain where persistent activity happens,” Vishwanathan says. Putting the neurons on a chip, however, gives scientists access to the cells without having to open skulls.

Vishwanathan and his colleagues may have gathered large amounts of very important data by eavesdropping on neuronal chatter, but researchers have begun to use microchips to talk back to the neurons. The microchips used by brain researchers are actually very similar to the ones found in most computers. Both neurons and microchips speak the same language since both use electricity to transmit information. This common language enables neurons and microchips to have a two-way conversation, in which the microchip monitors and records neuron activity, as well as telling neurons to fire or stay silent.

“If you want to understand how the brain functions, you need to develop technologies that let you record from large networks of brain cells,” said Naweed Syed, a neuroscientist at the University of Calgary in Alberta, Canada. The neurochip is one of those technologies.

To create a neurochip, scientists use sticky proteins to glue neurons to a microchip that contains large numbers of transistors and capacitors in a square millimeter. The transistors record the neurons’ electrochemical signals, while the capacitors can provide a small electric current to stimulate the neuron. By watching how neurons send and receive signals on the chip, scientists can identify the activity pattern for different types of brain cells. Knowing how healthy neurons behave may one day allow neurochips to intervene when this activity becomes unhealthy in diseases like Parkinson’s and Alzheimer's.

In Parkinson’s disease, neurons fire incorrectly due to the lack of dopamine, a neurotransmitter that carries the electrical signal across the tiny gap between neurons known as a synapse. People have tried to correct this deficit by supplementing the dopamine in the brain or by using electrodes to stimulate neurons deep in the brain. Although both of these techniques have good short-term effects, they aren’t as effective in the long run. Implanting a neurochip into the brain of a Parkinson’s patient could stimulate the neurons otherwise silenced by the lack of dopamine, but without the side effects of other treatments.

"Implanted chips could help restore lost [brain] function," said Stefano Vassanelli, a physiologist and neurochip expert at the University of Padua in Italy. "With electrical stimulation, you can more or less restore normal activity."

This type of thing may seem like science fiction, Syed said, but it could be reality sooner than we think. Still, years or even decades will probably pass before a person is actually treated with an implanted neurochip. In the meantime, scientists are using these chips in a variety of ways that are providing results today. Both Syed and Vassanelli believe that neurochips will provide a cheaper way to test the efficacy of new drugs, as well as monitor for side effects.

"These chip technologies enable us to understand how Mother Nature puts things together," Syed said. "Then we can simulate and recapitulate some of nature’s mystery."