杏仁核外侧BDNF神经元通过抑制弓状核AgRP神经元而控制摄食

大脑BDNF在能量稳态调节中扮演关键角色。BDNF通过抑制摄食和促进能量消耗维持能量稳定。BDNF在体重调节中的作用研究目前主要集中在下丘脑内，但关于下丘脑和脑干外BDNF是否也参与调节能量平衡，并不清楚。申请者最近研究表明：在下丘脑外某些脑区敲除BDNF后增加小鼠食欲，而在杏仁核外侧重新表达BDNF后小鼠恢复正常食欲。此外，BDNF的缺失突变增加AgRP表达水平。这些结果提示杏仁核外侧BDNF神经元可能通过抑制弓状核AgRP神经元活性而控制摄食。弓状核AgRP神经元在增加食欲和促进摄食中发挥核心作用，但AgRP神经元与BDNF神经元之间的联系，目前没有报道。因此，本研究不仅阐明BDNF在下丘脑外其它脑区参与调节能量稳态，也将解析杏仁核外侧BDNF神经元与弓状核AgRP神经元之间的环路连接，并首次提供证据表明两者之间的功能联系。

BDNF, brain derived neurotrophic factor, is a key player in the control of energy homeostasis. Substantial evidence has shown that BDNF regulates energy homeostasis through suppressing food intake as well as promoting energy expenditure. To date, predominant attention has been turned to the hypothalamus about the functional role for BDNF in energy homeostasis. Nevertheless, it remains unknown whether BDNF outside the hypothalamus and the brainstem is involved in the control of energy homeostasis. In my recent study, deletion of BDNF in some extrahypothalamic regions increased food intake, whereas re-expression of BDNF in the basolateral amygdala (BLA) of BDNF mutant mice restored their food intake back to the same level as their control littermates. Furthermore, the expression of AgRP (Agouti-related protein) increased in response to BDNF deletion. Collectively, these results suggest that BDNF neurons in the BLA might regulate feeding through suppressing AgRP neurons. AgRP neurons in the arcuate play a critical role in stimulating appetite and food intake. Thus far, however, there is no neural circuit reportedly linking AgRP neurons with BDNF neurons in feeding control. Hence, this proposed study will demonstrate not only a functional role for the extrahypothalamic BDNF in energy homeostasis, but also a neural circuit between BLA BDNF neurons and AgRP neurons.