Caltech scientists engineer supersensitive receptor, gain better understanding of dopam...( PASADENA Calif.--Genetically modifyi...)

PASADENA, Calif.--Genetically modifying a receptor found on the neurons that produce the neurotransmitter dopamine has given California Institute of Technology (Caltech) researchers a unique glimpse into the workings of the brain's dopamine system--as well as a new target for treating diseases that result from either too much or too little of this critical neurotransmitter.

Caltech scientists Henry Lester, Bren Professor of Biology, and Ryan Drenan, senior postdoctoral scholar in biology, worked with colleagues from Caltech, the University of Colorado at Boulder, the Rockefeller University, the University of Utah, and the pharmaceutical company Targacept. They genetically modified a type of brain receptor known as an "α6-containing nicotinic acetylcholine receptor" to make it more sensitive to both nicotine and acetylcholine. (Acetylcholine is another of the brain's neurotransmitters.)

The receptor in question is found primarily on neurons that produce the neurotransmitter dopamine. When the receptor is kicked into action by the presence of either nicotine or acetylcholine--two of the keys that fit its biochemical lock--the receptor prompts the neurons on which it sits to begin pumping out dopamine.

While previous studies of this same receptor had shown what happens when you block its function--when you put the brakes on dopamine production--this was the first time anyone was able to look at what happens when you make the receptor more sensitive and thus put the dopamine system into overdrive. "We were able to not only isolate this receptor's function, but also to amplify it," says Drenan, "and that allowed us to see exactly what it and it alone is capable of doing in the brain."

As it turns out, it's capable of doing a lot. Revved up by even low doses of nicotine, these receptors prompt the neurons on which they are clustered to let loose with a flood of dopamine. This flooding was obvious from the behavior of mice carr
'/>"/>