小鼠岛叶皮层功能偏侧性的细胞及环路机制研究

人脑功能的偏侧性（左右不对称性）是人类作为生物体适应外界环境的重要属性，该属性已被大量脑功能成像等数据证实。但是，对于人脑功能产生偏侧性的内在机制还知之甚少。岛叶皮层（IC）是味觉及内脏信息的初级感觉皮层，也是脑内整合内、外感受产生情感意识的重要神经枢纽。我们在对小鼠岛叶皮层前部（aIC）的研究中发现，aIC在感知内脏不适刺激时具有明显不对称性，以右侧aIC激活为主。通过光遗传及药物遗传手段单独激活右侧aIC或者右侧aIC到下丘脑外侧区（LHA）的纤维末梢能抑制摄食行为，抑制aIC或其到LHA末梢能促进摄食。而单独激活左侧aIC或其到LHA末梢则无此作用。后续基因组测序及病毒示踪结果提示左右侧aIC存在分子及环路的差异。因此，我们希望结合单细胞测序、病毒示踪、光遗传学、行为学及光纤记录等技术明确左右侧aIC功能差异的分子、细胞及环路机制，该研究也将有助于我们了解人脑功能偏侧性的内在机制。

Functional lateralization (left-right asymmetry) of human brain is the essential property of human beings adapted to the external environment as a living body, and it has been confirmed by a large number of data with brain imaging. However, the underlying mechanism of asymmetry is still largely unknown. The insular cortex is an important hub in the brain that senses the visceral and taste stimuli and integrates the inner and outer feelings and emotional awareness. Interestingly, we recently found that the caudal segment of the anterior part of insular cortex (caIC) in the mice showed obviously lateralized responses to the discomfort visceral stimulation, with the right, but not the left, insular cortex being significantly activated. In addition, optogenetic activation of the excitatory neurons in the right caIC or the nerve terminals projected from the right caIC to the right lateral hypothalamic area (LHA), but not activation of the left one, leads to the inhibition of feeding behavior. In summary, we hypothesize that the insular cortex in the mice has cellular and/or circuitry lateralization. Through the combination of techniques, such as optogenetic, DREADD, genomic and single-cell sequencing, behavioral testing and fiber photometry, we plan to further certificate the functional differences between the left and right insular cortex in the mice, and then explore the underlying neural circuits and molecular mechanisms. This study will contribute to our understanding of the mechanisms of the human brain lateralization.