[Abstract Title]. - Society for Neuroscience

Abstract: Cold temperatures are known to activate a small subset of sensory neurons, yet the
perception of cold varies from innocuously cool to painfully cold. Remarkably, even with this
diversity of cold responses, the majority are mediated by a single molecular sensor, the cold and
menthol receptor TRPM8. We are interested in understanding how TRPM8 mediates the diverse
sensations of cold, and have shown previously that TRPM8 neurons are anatomically
heterogeneous in vivo. Our data suggests that TRPM8 neurons comprise multiple and
functionally distinct neural circuits. To address this hypothesis, here we use expression of the
immediate early gene c-Fos and examine neural activity evoked by both cooling compounds and
cold temperatures in second order neurons in the spinal cord dorsal horn. Specifically, we found
that the super-cooling agent icilin, a TRPM8 agonist, induces robust c-Fos expression in the
superficial laminae of the dorsal horn when applied to the mouse hindpaw. These observations
were extended to activity evoked by a range of cold stimuli and the dependence of these
responses on functional TRPM8 expression. These data will begin to define and characterize the
neural circuitry responsible for the wide array of sensations evoked by cold.
Disclosures: W.M. Knowlton, None; D.D. McKemy, None.
Poster
265. Nociceptors II
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 265.3/EE4
Topic: B.02.t. TRP Channels
Support: NIH/NINDS Grant NS054069
Title: Mechanisms underlying TRPM8 adaptation
Authors: *R. L. DANIELS 1 , Y. TAKASHIMA 1 , H. N. WATERS 2 , E. R. LIMAN 2 , D. D.
MCKEMY 2 ;
1 Prog Neurosci., 2 Biol. Sciences, Neurobio. Section, USC, Los Angeles, CA
Abstract: Cold-sensing peripheral nerve fibers participate in innocuous temperature detection
and underlie thermoregulatory behaviors in many organisms. During a prolonged cold stimulus,
the firing rate of these fibers steadily decreases over time, an adaptive process thought to provide
the peripheral nervous system with a means to discriminate subtle changes in temperature. At the
molecular level, cold temperatures below 26°C are detected by TRPM8, a nonselective cation
channel that is expressed in a subset of peripheral afferent fibers. Recombinant TRPM8 channels
also adapt to prolonged cold stimuli with a time course similar to that observed with cold fibers,
a finding which suggests that adaptation occurs by reduced TRPM8 activity. Previous studies