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
The findings were published today in the online edition of
"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
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
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