Division of Biology and Biological Engineering, California Institute of Technology, 1200 East California Boulevard, M/C 156-29, Pasadena, CA 91125, USA.
Allen Institute for Brain Science, 551 North 34th Street, Suite 200, Seattle, WA 98103, USA.
Cell. 2014 Jan 30;156(3):522-36. doi: 10.1016/j.cell.2013.12.040.
The extended amygdala has dominated research on the neural circuitry of fear and anxiety, but the septohippocampal axis also plays an important role. The lateral septum (LS) is thought to suppress fear and anxiety through its outputs to the hypothalamus. However, this structure has not yet been dissected using modern tools. The type 2 CRF receptor (Crfr2) marks a subset of LS neurons whose functional connectivity we have investigated using optogenetics. Crfr2(+) cells include GABAergic projection neurons that connect with the anterior hypothalamus. Surprisingly, we find that these LS outputs enhance stress-induced behavioral measures of anxiety. Furthermore, transient activation of Crfr2(+) neurons promotes, while inhibition suppresses, persistent anxious behaviors. LS Crfr2(+) outputs also positively regulate circulating corticosteroid levels. These data identify a subset of LS projection neurons that promote, rather than suppress, stress-induced behavioral and endocrinological dimensions of persistent anxiety states and provide a cellular point of entry to LS circuitry.
杏仁复合体的延伸部分在恐惧和焦虑的神经回路研究中占据主导地位，但隔海马轴也起着重要作用。外侧隔核（LS）被认为通过其对下丘脑的输出来抑制恐惧和焦虑。然而，这个结构尚未使用现代工具进行剖析。2 型 CRF 受体（Crfr2）标记了 LS 神经元的一个亚群，我们使用光遗传学研究了它们的功能连接。Crfr2（+）细胞包括 GABA 能投射神经元，它们与下丘脑前区相连。令人惊讶的是，我们发现这些 LS 的输出增强了应激诱导的焦虑行为测量。此外，Crfr2（+）神经元的短暂激活促进，而抑制则抑制，持久的焦虑行为。LS Crfr2（+）输出也正向调节循环皮质醇水平。这些数据确定了 LS 投射神经元的一个亚群，它们促进而不是抑制应激诱导的持久焦虑状态的行为和内分泌学维度，并为 LS 回路提供了一个细胞进入点。
