1250 Broadway, 27th Floor New York, NY 10001


How the tongue keeps its tastes straight

Signals sent by tongue's taste cells prevent the brain from confusing bitter and sweet tastes

Columbia University Medical Center

New research at Columbia University Medical Center (CUMC) has revealed how special molecules help the tongue communicate with the brain to identify the correct taste. Using this knowledge, scientists were able rewire the taste-system of mice to perceive sweet stimuli as bitter tastes, and vice versa. The discovery provides new insights into how the tongue keeps its sense of taste organized despite the rapid turnover of the cells in its taste buds.

The findings were published today in the online edition of Nature.

"All of the tastes we experience are a combination of some or all of the five basic taste qualities, so there's little room for error," said study leader Charles S. Zuker, PhD, professor of biochemistry and molecular biophysics and of neuroscience and a Howard Hughes Medical Institute Investigator at CUMC, and principal investigator at Columbia's Zuckerman Institute. "An organism's survival can depend on its ability to distinguish attractive tastes like sweet from aversive ones like sour and bitter."

Humans perceive taste through thousands of tiny sensory organs called taste buds, which are located mostly on the upper surface of the tongue. Each taste bud contains 50 to 100 taste cells, which contain molecules, known as receptors, that can detect each type of taste -- sweet, bitter, sour, salty, or umami (savory). These taste cells then relay this information from the tongue to the brain.

"Most portions of the brain circuits that govern taste are hardwired at birth, except in the tongue, where the cells in our taste buds--taste receptor cells--connect to taste neurons," said co-lead author Hojoon Lee, PhD, an associate research scientist in the department of biochemistry and molecular biophysics at CUMC. "It's a highly dynamic process. Taste cells are replaced every one to three weeks, and one type of receptor may be replaced by a different type. Each time a new taste receptor cell is made, it needs to make the right connection with the brain."

The researchers wondered how the right connections are maintained when there's such a fast and random turnover of taste cells. They hypothesized that when taste receptor cells are produced, the cells most likely express dedicated molecular signals that attract the right complement of taste neurons.

To identify these signals, the CUMC team compared the gene expression of taste receptor cells, focusing on the two most dissimilar types: bitter and sweet. The researchers found that the two types of taste cells differed most strikingly in their expression of semaphorins, a family of proteins that help create neural circuits. While bitter receptors expressed large amounts of the Semaphorin 3A variant, sweet receptors expressed large amounts of Semaphorin 7A.

To determine whether these molecules guide taste receptor-to-neuron connectivity, the CUMC team genetically engineered two types of mice: one in which bitter receptors expressed Semaphorin 7A, the type normally produced by sweet receptors, and a second in which sweet receptors were modified to express Semaphorin 3A, the type produced by bitter receptors. The researchers hypothesized that the bitter receptors in the first model would now activate sweet neurons while sweet receptors in the second model would connect to bitter neurons.

"That's exactly what we observed," said Dr. Lee. "What this means is that taste receptor cells are determining their own connectivity by providing instructive signals to neurons."

The researchers conducted an additional experiment to confirm that the receptors had been rewired in the brain by switching the semaphorins. Mice whose bitter receptors were engineered to express the sweet semaphorin were presented with both plain water and bitter-tasting water. Unlike the normal controls, "the engineered mice did not avoid the bitter water" said Dr. Lee.

The researchers are currently studying the signaling molecules and connectivity of sour, salty, and umami taste receptors.

"The taste system gives us a unique opportunity to explore how connections between taste cells and neurons are wired and preserved, in the face of random turnover of our sensory cells" said Dr. Zuker. "Step-by-step studies like this one are helping us decipher the wiring rules of one of our most basic of our senses."


The study is titled, "Rewiring the Taste System." The other contributors are: Camilo A. Parada (CUMC) and Nicholas J.P. Ryba (National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD).

The other authors are Lindsey J. Macpherson (CUMC), Camilo A. Parada (CUMC), and Nicholas J.P. Ryba (NIH).

The study was supported by grants from funds the National Institute On Drug Abuse (R01DA035025). The authors declare no financial or other conflicts of interests.

Columbia University's Mortimer B. Zuckerman Mind Brain Behavior Institute brings together an extraordinary group of world-class scientists and scholars to pursue the most urgent and exciting challenge of our time: understanding the brain and mind. A deeper understanding of the brain promises to transform human health and society. From effective treatments for disorders like Alzheimer's, Parkinson's, depression and autism to advances in fields as fundamental as computer science, economics, law, the arts and social policy, the potential for humanity is staggering. To learn more, visit: zuckermaninstitute.columbia.edu.

Columbia University Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. The campus that Columbia University Medical Center shares with its hospital partner, NewYork-Presbyterian, is now called the Columbia University Irving Medical Center. For more information, visit cumc.columbia.edu or columbiadoctors.org.