Abnormal temperature and pain sensation is a common symptom of patients after stroke, and in some cases can lead to central pain syndrome, a debilitating disorder. Plasticity in neocortical circuits may play an important role in this disease. Here we will use sophisticated molecular tools and state-of-the-art recording techniques to identify the primary neocortical area representing pain and temperature stimuli in mice. Experiments will focus on cold sensation mediated by the TrpM8 receptor. TrpM8 is the sole receptor required for thermal sensation from ~10-24o C, and animals genetically lacking TrpM8 have a lack of temperature sensation in this range. In addition to cold temperature, TrpM8-expressing neurons are excited by the chemical ligand menthol, offering complementary routes for specific receptor activation. Our preliminary data indicate that TrpM8 stimulation specifically activates neurons in the posterior insula and that this activation is absent in TrpM8 receptor knock-out mice. We will use cold- or menthol stimulation in fosGFP transgenic mice followed by 2-photon targeted in vivo recordings of fosGFP+ neurons to determine the receptive field properties of cold-activated neurons. These experiments will lay a critical foundation for understanding how pain and temperature circuitry in the neocortex can be modified by experience and disease.
Pain encompasses both the sensation of noxious stimuli, as well as the emotionally aversive response to those stimuli. Although scientists have learned a great deal about how pain is encoded by peripheral neurons and the spinal cord, the way that pain is represented in the cerebral cortex of mammals has been controversial - a significant hurdle in understanding and treating pain disorders. Here we focus on a well-defined subset of thermal and noxious thermal sensation: cold sensation, in order to identify the specific neocortical representation of this stimulus. These studies will take advantage of molecular genetic tools and targeted recordings in mice. Our experiments will resolve long-standing questions about how pain and temperature information are mapped in the cerebral cortex, and will provoke new insight into the treatment of central pain disorders.