Dissecting a neural substrate for stress-induced analgesia

点击翻译按钮获取中文摘要

ABSTRACT Affective modulation of pain is an important mechanism for selecting appropriate behavior given different contexts. As an adaptive mechanism, it can aid an animal in surviving a life-threatening situation. Stress-induced analgesia (SIA) is such a phenomenon in which an affective state of high stress, induced by such stimuli as predator odor, produces analgesia to noxious stimuli. Previous studies of SIA have shown that stressful stimuli increase freezing behavior and decrease nociceptive responses, a readout of analgesia. Furthermore, SIA was shown to critically depend on the central amygdala (CeA). CeA is known to have a multitude of roles in processing emotional responses to pain and fear. The question is whether CeA is involved in producing true analgesia, or its role on eliciting freezing renders animals to show less motor responses to pain. Recent advances from others and our lab have discovered two distinct CeA neuronal populations for controlling freezing versus analgesia, respectively. Specifically, somatostatin-positive cells within the CeA (CeASST) have been shown by numerous groups to mediate freezing behavior, while our lab has discovered a population of cells activated by general anesthetics (CeAGA) which produces robust analgesia when optogenetically stimulated. Using predator odor as a model of SIA, I will assess the contribution of CeASST-freezing neurons versus CeAGA neurons in this model. Furthermore, preliminary studies revealed that CeAGA cells receive strong projections from a region called the amygdala-piriform transition zone (AmPir), and this region is known to be activated by predator odor. I will therefore further test the hypothesis that the AmPir-to-CeA circuit relays predator odor information to CeA to produce SIA. I will accomplish these aims through the use of transgenic mouse lines and viral strategies to target behaviorally-specific neural populations and optogenetically manipulate them during predator odor SIA. This proposal will provide novel insights into the neural circuits mediating the interplay between stress and pain, and advance our understandings of how emotions modulate pain.