Brain’s chemical signals seen in real time

From Nature:

Kleinfeld Lab, UC San Diego

Glowing neurotransmitters (in blue and green) seen through a ‘window’ into a mouse’s brain.

Neuroscientists have invented a way to watch the ebb and flow of the brain’s chemical messengers in real time. They were able to see the surge of neurotransmitters as mice were conditioned — similarly to Pavlov’s famous dogs — to salivate in response to a sound.

The study, presented at the American Chemical Society’s meeting in Philadelphia, Pennyslvania, on 22 August, uses a technique that could help to disentangle the complex language of neurotransmitters. Ultimately, it could lead to a better understanding of brain circuitry.

The brain’s electrical surges are easy to track. But detecting the chemicals that drive this activity — the neurotransmitters that travel between brain cells and lead them to fire — is much harder. “There’s a hidden signalling network in the brain, and we need tools to uncover it,” says Michael Strano, a chemical engineer at the Massachusetts Institute of Technology in Cambridge.

In many parts of the brain, neurotransmitters can exist at undetectably low levels. Typically, researchers monitor them by sucking fluid out from between neurons and analysing the contents in the lab. But that technique cannot measure activity in real time. Another option is to insert a metal probe into the space between neurons to measure how neurotransmitters react chemically when they touch metal. But the probe is unable to distinguish between structurally similar molecules, such as dopamine, which is involved in pleasure and reward, and noradrenaline which is involved in alertness.

Enter neuroscientist Paul Slesinger of the Icahn School of Medicine at Mount Sinai in New York City and neurophysicist David Kleinfeld of the University of California, San Diego. In May, they reported a method for making genetically modified human cells that produce artificial receptors for neurotransmitters. These …

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