Last updated on March 16, 2014 at 1:21 EDT


March 11, 2011





Uncovering Rare Receptors


Bartfai’s group has long been interested in a class of nerve cells in the brain called “warm sensitive neurons.” These cells sense and respond to changes in body temperature, acting like a thermometer inside the brain. As body temperature increases, warm sensitive neurons become more active, telling the body to bring its temperature down. Without this regulation, body temperature could reach dangerous levels, even leading to death.

In the past 60 years, scientists had identified about a dozen receptors on warm sensitive neurons that regulate these nerve cells’ activity. But Bartfai wanted to find additional receptors to better understand how the cells function.


Sequencing Single Neurons

Bartfai and Eberwine took a unique approach to indentifying gene activity.


By matching the DNA sequences obtained to published sequences, the scientists were able to identify the corresponding genes, and thus which genes are turned “on” in the nerve cells.

The technique differs from commonly used methods for studying gene activity. Typically researchers “pool” neurons of one type and examine them as a group, rather than studying single cells. In addition, current techniques generally rely on searching for active genes using microarrays””a technique that relies on the preferential binding of sequences in the messenger RNAs /cDNAs to matching DNA sequences “spotted” on the microarray. However, these methods only detect RNAs for which “probes are present on the microarray,” in other words, those that are expected. Also, because of the lower sensitivity of this technique than sequencing, only the cDNAs cells produce in relatively large amounts are detected.

“Using single cells, rather than pooling, and sequencing, rather than microarrays, uncovers many more receptors active in neurons,” says Bartfai. “With other methods you miss receptors present in only a few copies. But that does not mean that they are not important.”

Revealing Neurons’ Complexity

Using their new method Bartfai and Eberwine identified more than 400 receptors active in warm sensitive neurons. About one-third of the receptors are so-called “orphan” receptors, meaning the chemicals they bind to are unknown. The rest were receptors whose ligands (substances they bind to) are known””among them, the authors found a few surprises.

For example, Bartfai and Eberwine discovered that the receptor responsible for binding insulin is active on warm sensitive neurons””something no one had previously suspected.

The insulin receptor is known to be involved in regulating a person’s metabolism. Follow-up studies by Bartfai’s group have now shown that insulin binds to receptors on warm sensitive neurons to decrease their activity, causing an increase in body temperature, or hyperthermia. Thus, insulin is a key regulator for both body metabolism and temperature.

“This study highlights the complexity of these cells by showing us the large number of different RNAs that are present,” said Eberwine.

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