Electrical Activity Alters Language Used By Nerve Cells

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Electrical Activity Alters Language Used By Nerve Cells

UC San Diego biologists have shown that the chemical language with

which neurons communicate depends on the pattern of electrical

activity in the developing nervous system. The findings suggest that

modification of nerve activity could have potential as a treatment

for a wide range of brain disorders.

In the study, published in the early on-line edition of the journal

Proceedings of the National Academy of Sciences, the biologists

showed that, contrary to the prevailing viewpoint,

neurotransmitters - the chemical language of nerve cells - and

receptors - the proteins that receive and respond to

neurotransmitters - are not specified by a rigid genetic program.

Altering nerve activity during development determines the " mother

tongue " nerve cells use to communicate. The study will appear in the

print edition of PNAS on January 2.

" Most cognitive disorders, such as depression, schizophrenia and

Parkinson's disease, involve problems with neurotransmitters or

neurotransmitter receptors, " said Spitzer, a professor of

biology and the senior author of the study. " If modifying electrical

activity in the adult brain can alter neurotransmitters and

receptors similarly to the way we have discovered in the developing

frog nervous system, it could provide a promising approach to

treating these disorders. "

In vertebrates including frogs and humans, nerves communicate with

muscles by releasing a neurotransmitter called acetylcholine.

Spitzer and Borodinsky, who was an assistant project scientist

working with Spitzer when she performed the research, wanted to know

if genetics is the only factor responsible for the selection of

acetylcholine as the language used in nerve to muscle communication,

or if other factors could play a role.

To find out, the researchers used drugs to increase and decrease the

electrical activity in nerve cells of frog embryos. These changes in

activity changed the identity of the neurotransmitter produced by

the nerve cells. Because the new chemical language being used by the

nerves would not be detected if the muscles continued to produce

only acetylcholine receptors, Spitzer and Borodinsky also looked for

changes in the muscle cells' transmitter receptors.

They discovered that, unlike in adult muscle, very early in

development the muscle cells actually make multiple types of

receptors, not just acetylcholine receptors. Remarkably,

neurotransmitter receptors on the muscle cells are selected to match

the neurotransmitter being produced by the nerve cells when early

activity is perturbed.

" Our discovery, that developing muscle cells express several

different types of neurotransmitter receptors, is surprising, " said

Borodinsky, who is now an assistant professor of physiology at the

U.C. School of Medicine. " The vertebrate neuromuscular

junction has been very well studied, and it has long been thought

that acetylcholine was the only neurotransmitter used there.

" Sometimes people studying development can be misled by knowing how

things work in an adult animal, " she added. " You have so much

information about the end point that you may not open your eyes to

what happens early on. "

The results show that the development of communication between

nerves and muscles is flexible. Rather than a genetic program

specifying that acetylcholine will be the language of communication,

it is one of several languages that nerve cells are capable of

using. Similarly, muscle cells have the potential to understand

several languages. During development, the level of electrical

activity in nerve cells determines which of many possible

neurotransmitter languages will be used.

" It may seem wasteful to start with multiple types of receptors, and

then eliminate the ones that aren't needed, " commented Spitzer. " But

it provides organisms with the ability to adapt to the environmental

conditions in which they are living. "

The researchers are not certain if the adult human brain will retain

this same flexibility, but experimental treatments involving

electrical stimulation of the brain are being used by other

researchers in clinical practice. Spitzer thinks this study provides

useful information for the researchers developing these therapies.

" Our research provides new insight about a way in which electrical

stimulation affects communication in the nervous system, " explained

Spitzer. " If electrical stimulation shows promise as a treatment,

understanding the mechanism by which it works should make it

possible to be much more selective about how and where to stimulate

the brain. "

The study was supported by the National Institutes of Health and the

National Science Foundation.