小柯机器人

美国国立卫生研究院国家酒精滥用和酒精中毒研究所Andrew Holmes和瑞士巴塞尔大学Andreas Lüthi团队合作的最新研究表明杏仁核中间神经元簇调控恐惧状态的转换。这一研究成果于2021年5月26日在线发表在国际学术期刊《自然》上。

通过体内钙成像、功能操作和生理学切片相结合的方法，研究人员发现小鼠杏仁核中间神经元（ITCs）的不同抑制簇在恐惧记忆的获取和恢复过程中发挥截然相反的作用。

此外，研究发现ITC簇通过突触抑制互相拮抗，并差异性调控功能不同皮质和中脑投射杏仁核的输出途径。该研究结果表明，ITC簇之间的活动平衡代表了一个独特的调节基序，可以协调分布式神经回路，进而调节高恐惧状态和低恐惧状态之间的转换。这些发现表明，ITC在一系列杏仁核功能和相关脑部状态转换过程中发挥广泛作用，从而增强了个体适应环境的能力。

据介绍，适应性行为是形成恐惧记忆所必需的，但这些记忆也可以被清除。有效的清除记忆可以防止对感知到威胁的过度和持续反应，例如焦虑症以及与“创伤和压力源有关”的疾病。然而， 尽管有证据表明恐惧记忆形成和清除是由不同的神经回路所介导，但对这些回路之间相互作用的机制仍知之甚少。

附：英文原文

Title: Intercalated amygdala clusters orchestrate a switch in fear state

Author: Kenta M. Hagihara, Olena Bukalo, Martin Zeller, Ayla Aksoy-Aksel, Nikolaos Karalis, Aaron Limoges, Tanner Rigg, Tiffany Campbell, Adriana Mendez, Chase Weinholtz, Mathias Mahn, Larry S. Zweifel, Richard D. Palmiter, Ingrid Ehrlich, Andreas Lthi, Andrew Holmes

Issue&Volume: 2021-05-26

Abstract: Adaptive behaviour necessitates the formation of memories for fearful events, but also that these memories can be extinguished. Effective extinction prevents excessive and persistent reactions to perceived threat, as can occur in anxiety and ‘trauma- and stressor-related’ disorders1. However, although there is evidence that fear learning and extinction are mediated by distinct neural circuits, the nature of the interaction between these circuits remains poorly understood2,3,4,5,6. Here, through a combination of in vivo calcium imaging, functional manipulations, and slice physiology, we show that distinct inhibitory clusters of intercalated neurons (ITCs) in the mouse amygdala exert diametrically opposed roles during the acquisition and retrieval of fear extinction memory. Furthermore, we find that the ITC clusters antagonize one another through mutual synaptic inhibition and differentially access functionally distinct cortical- and midbrain-projecting amygdala output pathways. Our findings show that the balance of activity between ITC clusters represents a unique regulatory motif that orchestrates a distributed neural circuitry, which in turn regulates the switch between high- and low-fear states. These findings suggest that the ITCs have a broader role in a range of amygdala functions and associated brain states that underpins the capacity to adapt to salient environmental demands.

DOI: 10.1038/s41586-021-03593-1

Source: https://www.nature.com/articles/s41586-021-03593-1

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
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