The Dissection of Pain Emotion Circuit Using the in Vivo Whole Cell Recording-based Strategy

Dissecting the brain circuits mediating the aversive and emotional component of pain is an essential direction for a comprehensive understanding of nociception. The central amygdala (CeA) is a key brain region in processing the emotional component of pain. Although great progress has been made, the specific CeA cell types and inputs/outputs mediating pain emotion are still not fully clarified. Here, we report for the first time in vivo whole cell recordings of CeA neurons in anesthetized mice, and demonstrate responsiveness to several different sensory modalities (thermal, mechanical, chemical, and auditory). We observed several distinct response profiles, including cells activated by all sensory stimuli, only a subset of stimuli, no response to any, and a small subpopulation that was inhibited by noxious stimuli. In ongoing studies, we are using tissue clearing and immunostaining to morphologically reconstruct recorded neurons and correlate in vivo activity patterns with known molecular markers of different CeA cell types (PKC-delta, somatostatin, dynorphin). We are also pursuing long-range circuit dissection with chemogenetics and transcranial optogenetics to identify the sources of sensory input to these cells. Together, our results will provide new insights into the CeA microcircuits underlying emotional pain processing, and establish a new in vivo paradigm for dissecting other functions of the CeA.