Georgia: The tiny fruit fly can help humans investigate the genetic and neural bases of detecting painful or harmful cold stimuli and offer intriguing, potential implications for human health, according to a new study. A team of researchers led by Dr. Daniel N. Cox, associate professor of neuroscience at Georgia State University, has discovered that fruit flies have cold-sensing neurons that when activated drive specific, aversive behaviors to damaging cold, which requires the function of evolutionarily conserved ion channels known as Transient Receptor Potential (TRP) channels.
In the journal Current Biology, the researchers establish the fruit fly, Drosophila melanogaster,
as a powerful genetic and behavioral model for unraveling questions
about the cellular and molecular bases of damaging cold perception,
which have not been well understood.
The study explores the concept of nociception, the peripheral and
central nervous systems’ perception of painful or potentially tissue
damaging stimuli, which is generated by activating sensory nerve cells
called nociceptors. This evolutionarily conserved process is critically
important for survival.
Nociception, coupled with pain sensation, alerts an organism to
possible environmental dangers and allows it to execute behavioral
responses to protect against incipient damage. Acute and chronic pain
can manifest as altered nociception in neuropathic pain states.
The study found that one of the implicated TRP channel genes called Pkd2
has been causally linked to autosomal dominant polycystic kidney
disease (PKD), the most common monogenic disease in humans. Pkd2 ion
channels appear to function as cold sensors and misexpression of Pkd2
can confer cold sensitivity to normally insensitive neurons. While it is
not yet known if PKD patients have cold nociception defects, these new
findings suggest this merits further investigation as a potential
These same cold-sensing neurons also function as mechanosensors for
touch, revealing that they, as well as the TRP channels identified in
this study, are multimodal and raising the question of how neurons and
ion channels distinguish between harmless and harmful stimuli to drive
specific behavioral responses. Using sophisticated optical assays of
neural activation by touch versus cold stimuli, the researchers
demonstrate that these sensory neurons have different activation
thresholds, with touch having a low threshold and cold having a high
threshold, that ultimately determine the appropriate behavioral
“This new model sets the stage for uncovering evolutionarily
conserved molecular control of nociception,” said Cox. “It also provides
a powerful genetic platform for unraveling the neural circuitry and
molecular mechanisms that integrate multimodal sensory input to produce
specific behaviors in response to diverse environmental stimuli.”
The research team included Kevin Armengol, Atit A. Patel, Nathaniel
J. Himmel, Luis Sullivan, Dr. Srividya C. Iyer and Dr. Eswar P.R. Iyer
of the Cox Lab at Georgia State’s Neuroscience Institute and Center for
Behavioral Neuroscience, and collaborators Heather N. Turner and Michael
J. Galko from MD Anderson Cancer Center.
The next steps will be to dissect the neural circuitry, additional
molecular players and synaptic mechanisms that modulate cold nociception
and multimodal sensory processing.