Smart trap: nanosensor tracks major brain chemical.The study of neurological diseases and brain functions could become much more precise with the invention of an optical sensor that can closely monitor a specific chemical amidst the brain's complex neurochemical neu·ro·chem·is·try
The study of the chemical composition and processes of the nervous system and the effects of chemicals on it.
Called glutamate glutamate /glu·ta·mate/ (gloo´tah-mat) a salt of glutamic acid; in biochemistry, the term is often used interchangeably with glutamic acid.
1. A salt of glutamic acid. , this neurotransmitter neurotransmitter, chemical that transmits information across the junction (synapse) that separates one nerve cell (neuron) from another nerve cell or a muscle. Neurotransmitters are stored in the nerve cell's bulbous end (axon). is secreted by nerve cells and influences processes ranging from sensory perception to learning and memory. It also plays a role in Alzheimer's and Parkinson's disease Parkinson's disease or Parkinsonism, degenerative brain disorder first described by the English surgeon James Parkinson in 1817. When there is no known cause, the disease usually appears after age 40 and is referred to as Parkinson's disease. .
Until recently, it has been almost impossible to study this transient chemical in action. However, Wolf Frommer of the Carnegie Institution at Stanford University and his colleagues recently designed a nanosensor with which they can track the release of glutamate by nerve cells.
Described in an upcoming Proceedings of the National Academy of Sciences The Proceedings of the National Academy of Sciences of the United States of America, usually referred to as PNAS, is the official journal of the United States National Academy of Sciences. , the nanosensor consists of several protein segments stitched together. The sensing part of the construct is derived from the bacterium Escherichia coli Escherichia coli (ĕsh'ərĭk`ēə kō`lī), common bacterium that normally inhabits the intestinal tracts of humans and animals, but can cause infection in other parts of the body, especially the urinary tract. . The protein segment changes shape when glutamate binds to it. The protein's two lobes, which are connected by a hinge, snap together like the jaws of a Venus flytrap.
To their sensing mechanism, the researchers attached two fluorescent jellyfish jellyfish, common name for the free-swimming stage (see polyp and medusa), of certain invertebrate animals of the phylum Cnidaria (the coelenterates). The body of a jellyfish is shaped like a bell or umbrella, with a clear, jellylike material filling most of the proteins, one that glows blue and one that glows yellow. In a process known as fluorescence resonance energy transfer Fluorescence resonance energy transfer (FRET) describes an energy transfer mechanism between two chromophores.
A donor chromophore in its excited state can transfer energy by a nonradiative, long-range dipole-dipole coupling mechanism to an acceptor chromophore in close , when one protein becomes excited by light, it both emits blue light and transfers energy to the other protein, causing it to produce yellow light.
"It's like having two musical tuning forks," says Frommer. "If you hit one fork and you bring the second one close enough to it without touching, the second fork will start to vibrate as well."
When the sensor binds to glutamate, a change in the nanosensor's configuration increases the distance between the two fluorescent proteins, Frommer suspects, reducing the amount of energy transferred from the blue to the yellow one.
In a display of finesse, Frommer and his colleagues genetically programmed rat brain cells to produce the nanosensors and anchor the constructs to the surfaces of their cell membranes. When the researchers gave the cells an electrical shock, the cells produced a spurt of glutamate that indeed tripped the nanosensors.
The scientists then observed a dimming of the yellow light. The more glutamate the cells released, the lower the ratio of that yellow light to the blue light.
"This is a major advance," says Robert Edwards, a neuroscientist at the University of California, San Francisco . "I think a lot of people will jump on this."
The nanosensor's location on the cell membranes currently prevents it from tracking glutamate inside the cells. Scientists next may program cells to place the sensor on internal structures to shed light on how they manufacture and deploy the neurotransmitter.
To observe glutamate in whole organisms, rather than only in individual ceils, the Stanford group is genetically programming the tiny worm Caenorhabditis elegans to produce the sensors. Eventually, the researchers plan to incorporate the sensors into mice and to use an optical-imaging system to detect changes in fluorescence that would correlate with neural activity.