Electrophysiological studies have demonstrated that increases in the excitability of amygdala neurons correlate with short-term pain following injury, suggesting that hyperexcitability of neurons in the amygdala plays a critical role in the modulation of pain-related behaviors. A direct causal link between the changes in intrinsic excitability in the amygdala and the time-dependent alterations in affective behaviors following injury, however, has not been established. This project aims at addressing this question directly by performing whole-cell voltage- and current-clamp experiments in visually identified amygdala neurons in acute mouse brain slices obtained from animals in models of inflammatory and neuropathic pain. Behavioral approaches to measure mechanical and thermal hypersensitivity as well as anxiety-like and depression-like behaviors are used in combination with electrophysiological and molecular genetic techniques to define the physiological roles of molecularly distinct subpopulation of cells in the amygdala in the modulation of pain-related behaviors. Parallel western blot and immunohistochemical experiments aim at examining the expression pattern of endogenous molecular signaling proteins in amygdala neurons at different time points following injury. Further experiments aim at evaluating the physiological roles of individual molecules on long-term changes in distinct sensory and affective behaviors following injury. This is the third year of this project. The accomplishments during this year include the identification and electrophysiological characterization of subpopulations of amygdala neurons that differentially contribute to pain-related behaviors. We have also been able to identify anatomical connections with the amygdala that may be involved in the modulation of pain-related behaviors.
