小鼠前岛叶皮层调控摄食行为的环路机制研究

Feeding behavior is the instinct response in mammals, which is controlled by the central nervous system. The hypothalamus is usually viewed as feeding center, which integrates both the internal and the external information to maintain the energy balance. However, under some pathological conditions, such as gastrointestinal discomfort or inflammation, appetite might drop and energy balance might be broken. It is possible that some other brain regions may sense these anorexic signals and regulate feeding via innervating the hypothalamus. Insular Cortex (IC) is a key region that severs as the primary visceral and gustatory cortex. Researches using fMRI imaging suggest that IC is involved in feeding behavior and disorder of IC is tightly related to anorexia nervosa in human. Our data demonstrate that glutamatergic neurons in anterior Insular Cortex (aICCaMKII+) were activated under certain pathological conditions. Activation of the aICCaMKII+ neurons using optogenetics reduces food intake and induces avoidance, while inhibition of the aICCaMKII+ neurons increases food intake and induces place preference. Virus tracing reveals that the aICCaMKII neurons projected directly to the vGluT2+ neurons in the lateral hypothalamus (LHA). Therefore, we hypothesized that aIC-LHA pathway may participate in the regulation of feeding disorders caused by certain pathological stimuli. This study will help us to understand the role of aIC in feeding behavior and its circuitry mechanisms, which may provide new targets for the treatment of eating disorders.

摄食行为是人类赖以生存的本能反应，受复杂的中枢机制调控。下丘脑被认为是摄食中枢，感受内外信息，维持能量平衡。但是，在某些病理条件下，如胃肠道不适或炎症等，食欲明显下降，能量平衡被打破。是否存在其它脑区可以感受伤害性刺激，并操纵下丘脑引起摄食障碍？岛叶皮层被认为是初级味觉及内脏感觉中枢。大量人脑功能磁共振研究提示，岛叶参与摄食行为，其活性的失调还可能是神经性厌食的重要因素。我们预实验结果发现，某些引起内脏不适的病理性刺激可以特异性激活前岛叶皮层谷氨酸能神经元(aICCaMKII+)。光遗传激活(抑制)aICCaMKII+可以引起摄食下降(增加)。示踪结果显示aICCaMKII+直接投射到外侧下丘脑区vGluT2阳性神经元。因此，我们提出假设，aIC可能通过LHA参与调控某些病理刺激导致的摄食障碍。这一研究将有助于我们了解aIC在摄食行为中的作用及其环路基础，并为治疗摄食障碍提供新的靶点。

摄食行为是人类赖以生存的本能反应，受复杂的中枢机制调控。下丘脑被认为是摄食中枢，感受内外信息，维持能量平衡。但是，在某些病理条件下，如胃肠道不适或炎症等，食欲明显下降，能量平衡被打破。岛叶皮层被认为是初级味觉及内脏感觉中枢。大量人脑功能磁共振研究提示，岛叶参与摄食行为，其活性的失调还可能是神经性厌食的重要因素。我们经过研究发现，引起内脏不适的病理性刺激可以特异性激活前岛叶皮层谷氨酸能神经元(aICCaMKII+)。光遗传激活(抑制)aICCaMKII+可以引起摄食下降(增加)。追踪结果发现，aICCaMKII+神经元直接投射到外侧下丘脑区vGluT2阳性神经元。该投射参与调控病理刺激导致的摄食障碍。这一研究有助于我们了解aIC在摄食行为中的作用及其环路基础，并为治疗摄食障碍提供新的靶点。