Distinct basolateral amygdala excitatory inputs mediate the somatosensory and aversive-affective components of pain

作者：Xiaojing Meng, Lingxiao Yue, An Liu, Wenjuan Tao, Li Shi, Wan Zhao, Zhongmin Wu, Zhi Zhang, Liecheng Wang, Xulai Zhang, Wenjie Zhou · 发表于：Journal of Biological Chemistry · 年份：2022 · DOI：10.1016/j.jbc.2022.102207 · 被引用次数：31 · 研究领域：Pain Mechanisms and Treatments、Neurotransmitter Receptor Influence on Behavior、Stress Responses and Cortisol

Pain is a multidimensional perception that includes unpleasant somatosensory and affective experiences; however, the underlying neural circuits that mediate different components of pain remain elusive. Although hyperactivity of basolateral amygdala glutamatergic (BLA Glu ) neurons is required for the somatosensory and emotional processing of pain, the precise excitatory inputs to BLA Glu neurons and their roles in mediating different aspects of pain are unclear. Here, we identified two discrete glutamatergic neuronal circuits in male mice: a projection from the insular cortex glutamatergic (IC Glu ) to BLA Glu neurons, which modulates both the somatosensory and affective components of pain, and a projection from the mediodorsal thalamic nucleus (MD Glu ) to BLA Glu neurons, which modulates only the aversive-affective component of pain. Using whole-cell recording and fiber photometry, we found that neurons within the IC→BLA and MD→BLA pathways were activated in mice upon inflammatory pain induced by injection of complete Freund's adjuvant (CFA) into their paws. Optical inhibition of the IC Glu →BLA pathway increased the nociceptive threshold and induced behavioral place preference in CFA mice. In contrast, optical inhibition of the MD Glu →BLA pathway did not affect the nociceptive threshold but still induced place preference in CFA mice. In normal mice, optical activation of the IC Glu →BLA pathway decreased the nociceptive threshold and induced place aversion, while optical ...