In:
eLife, eLife Sciences Publications, Ltd, Vol. 4 ( 2015-09-11)
Abstract:
Learning is critical to survival for humans and other animals. The learning process is regulated by receptors on the surface of brain cells called N-Methyl-D-aspartate receptors (or NMDA receptors for short). These receptors help to strengthen signals between brain cells, which allows a new concept or action to be learned. However, it has been difficult to pin down how the role of NMDA receptors selectively in specific types of brain cells. While drugs can be used to quickly block NMDA receptors throughout the brain, it is hard to target drugs to a specific cell type. Also, genetic engineering can be used to selectively knock out NMDA receptors in certain types of brain cells, but these techniques are too slow, and can take weeks or even a lifetime to work. Now, Yang et al. have developed a clever way to combine an NMDA-blocking drug and genetic engineering to study NMDA receptors' responses to cocaine in specific brain cells. This approach involved first creating an inactive form of an NMDA-blocking drug that can only becomes active when it is processed by an enzyme that is normally produced in pigs' livers. Next, living mouse brain cells, including some that were engineered to express the pig enzyme, were exposed to the drug in the laboratory. The drug blocked the NMDA receptors on brain cells that expressed the enzyme, but not the receptors on nearby brain cells that lacked the enzyme. This occurred even though all the cells produced NMDA receptors and all were exposed to the drug. NMDA receptors have been known to play an important role in cocaine addiction for more than 20 years. Drugs like cocaine can co-opt the normally healthy learning process involving NMDA receptors and lead to a maladaptive form of learning that is commonly called addiction. Cocaine strengthens signals between brain cells causing the behaviors associated with using cocaine to become deeply ingrained and difficult to change. Yang et al. used cell type-specific targeting of a drug that blocks NMDA receptors to observe what happened in cocaine-exposed brain cells with, or without, working NMDA receptors. As expected, the experiments showed that cocaine didn't strengthen brain signals in cells without working NMDA receptors. Specifically, the experiments showed that NMDA receptors on a type of brain cell that release a pleasure-inducing chemical called dopamine are necessary for cocaine–induced synaptic plasticity. The combination technique developed by Yang et al. will likely be used by other scientists to further study the role of NMDA receptors in specific brain cells during addiction and normal brain activity.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.10206.001
DOI:
10.7554/eLife.10206.002
DOI:
10.7554/eLife.10206.003
DOI:
10.7554/eLife.10206.004
DOI:
10.7554/eLife.10206.005
DOI:
10.7554/eLife.10206.006
DOI:
10.7554/eLife.10206.007
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2015
detail.hit.zdb_id:
2687154-3
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