Yu Kai, Garcia da Silva Pedro, Albeanu Dinu F, Li Bo
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, and.
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, and Champalimaud Neuroscience Program, Champalimaud Centre for the Unknown, Lisbon 1400-038, Portugal.
J Neurosci. 2016 Jun 15;36(24):6488-96. doi: 10.1523/JNEUROSCI.4419-15.2016.
The central amygdala (CeA) has a key role in learning and expression of defensive responses. Recent studies indicate that somatostatin-expressing (SOM(+)) neurons in the lateral division of the CeA (CeL) are essential for the acquisition and recall of conditioned freezing behavior, which has been used as an index of defensive response in laboratory animals during Pavlovian fear conditioning. However, how exactly these neurons participate in fear conditioning and whether they contribute to the generation of defensive responses other than freezing remain unknown. Here, using fiber-optic photometry combined with optogenetic and molecular techniques in behaving mice, we show that SOM(+) CeL neurons are activated by threat-predicting sensory cues after fear conditioning and that activation of these neurons suppresses ongoing actions and converts an active defensive behavior to a passive response. Furthermore, inhibition of these neurons using optogenetic or molecular methods promotes active defensive behaviors. Our results provide the first in vivo evidence that SOM(+) neurons represent a CeL population that acquires learning-dependent sensory responsiveness during fear conditioning and furthermore reveal an important role of these neurons in gating passive versus active defensive behaviors in animals confronted with threat.
The ability to develop adaptive behavioral responses to threat is fundamental for survival. Recent studies indicate that the central lateral amygdala (CeL), in particular its somatostatin-expressing neurons, is crucial for both learning and the expression of defensive response. However, how exactly these neurons participate in such processes remains unclear. Here we show for the first time in behaving mice that the somatostatin-expressing neurons in the CeL acquire learning-dependent responsiveness to sensory cues predicting a threat. Furthermore, our results indicate that these neurons gate the behavioral output of an animal: whereas high activity in these neurons biases toward passive defensive responses, low activity in these neurons allows the expression of active defensive responses.
中央杏仁核（CeA）在防御反应的学习和表达中起关键作用。最近的研究表明，CeA外侧部（CeL）中表达生长抑素的（SOM(+)）神经元对于条件性僵住行为的获得和回忆至关重要，在巴甫洛夫恐惧条件反射过程中，条件性僵住行为已被用作实验动物防御反应的指标。然而，这些神经元究竟如何参与恐惧条件反射，以及它们是否除了僵住之外还对其他防御反应的产生有贡献，仍然未知。在这里，我们在行为小鼠中使用光纤光度法结合光遗传学和分子技术，表明SOM(+) CeL神经元在恐惧条件反射后被预测威胁的感觉线索激活，并且这些神经元的激活会抑制正在进行的动作，并将主动防御行为转变为被动反应。此外，使用光遗传学或分子方法抑制这些神经元会促进主动防御行为。我们的结果提供了首个体内证据，表明SOM(+)神经元代表了CeL中的一个群体，该群体在恐惧条件反射过程中获得依赖学习的感觉反应性，并且进一步揭示了这些神经元在控制面对威胁的动物的被动与主动防御行为方面的重要作用。
发展对威胁的适应性行为反应的能力是生存的基础。最近的研究表明，中央外侧杏仁核（CeL），特别是其表达生长抑素的神经元，对于防御反应的学习和表达都至关重要。然而，这些神经元究竟如何参与这些过程仍不清楚。在这里，我们首次在行为小鼠中表明，CeL中表达生长抑素的神经元获得了对预测威胁的感觉线索的依赖学习的反应性。此外，我们的结果表明，这些神经元控制动物的行为输出：这些神经元的高活动偏向于被动防御反应，而这些神经元的低活动则允许主动防御反应的表达。
