哈佛医学院Gord Fishell小组近日取得一项新成果。经过不懈努力，他们提出了外侧隔区中的特征特异性威胁编码指导防御行为。2026年5月20日出版的《自然》发表了这项成果。

在这里，研究人员将重点放在表达2型CRH受体（LS^Crhr2）的LS神经元群体上，该神经元亚群对小鼠的状态依赖性行为变化和威胁反应至关重要。该课题组人员将单细胞钙成像、分子测序和电路解剖相结合，以揭示所涉及的细胞类型的空间和功能组织、它们执行的计算以及它们的上游激活子传递的信息。课题组研究人员确定LS^Crhr2种群活动是线索驱动的防御行动所必需的，通过快速和动态地编码威胁表征来预测行为结果。

该研究组发现这些威胁表征是由不同的LS^Crhr2亚类（由它们的分子特征、空间位置和输入架构定义）差异表示的各种威胁信号的收敛形成的。值得注意的是，这些反应反映了海马和下丘脑分别优先传递线索和动作相关信号的特定传入事件。这些发现建立了一个多特征的组织原则，该原则是LS如何调节响应环境挑战的动机行为的基础。

据了解，快速检测和评估潜在威胁的能力对生存至关重要，需要将感官信息与内部状态和先前的经验相结合。侧隔（LS）——边缘前脑中的一种抑制结构——被认为整合这些高阶认知信号来调节防御反应。然而，这一过程的基本细胞、电路和计算机制仍然未知。

附：英文原文

Title: Feature-specific threat coding in lateral septum guides defensive action

Author: Bhatti Mazo, Dionnet Leandro, Berger, Marc Z. C., Pasqualini, Amanda Loren, Wu, Sherry Jingjing, Reid, Christopher M., Brito, Salvador Ignacio, Qiu, Shenfeng, Levitt, Pat, Anthony, Todd Erryl, Fishell, Gord

Issue&Volume: 2026-05-20

Abstract: The ability to rapidly detect and evaluate potential threats is essential for survival and requires the integration of sensory information with internal state and previous experience. The lateral septum (LS)—an inhibitory structure in the limbic forebrain—is thought to integrate these higher-order cognitive signals to regulate defensive responses1,2. However, the cellular, circuit and computational mechanisms fundamental to this process remain unknown. Here we focus on the population of LS neurons that express the type 2 CRH receptor (LSCrhr2), a neuronal subset shown to be critical for state-dependent behavioural changes and threat responsivity3,4,5,6,7 in mice. We use a combination of single-cell calcium imaging, molecular sequencing and circuit dissection to reveal the spatial and functional organization of the cell types involved, the computations they perform and the information relayed by their upstream activators. We determine that LSCrhr2 population activity is required for cue-driven defensive actions by rapidly and dynamically encoding threat representations that predict behavioural outcomes. We find that these threat representations are formed through the convergence of various signals differentially represented by distinct LSCrhr2 subclasses, which are defined by their molecular features, spatial locations and input architectures. Notably, these responses reflect specific afferents from the hippocampus and hypothalamus that preferentially impart cue- and action-related signals, respectively. These findings establish a multifeatured organizational principle that underlies how the LS mediates motivated behaviours in response to environmental challenges.

DOI: 10.1038/s41586-026-10520-9

Source: https://www.nature.com/articles/s41586-026-10520-9