Intercalated amygdala clusters orchestrate a switch in fear state.
Intercalated amygdala clusters orchestrate a switch in fear state.
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DOI：
10.1038/s41586-021-03593-1
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发表时间：
2021-06
期刊：
影响因子：
64.8
通讯作者：
Holmes A
中科院分区：
文献类型：
--
作者：
Hagihara KM;Bukalo O;Zeller M;Aksoy-Aksel A;Karalis N;Limoges A;Rigg T;Campbell T;Mendez A;Weinholtz C;Mahn M;Zweifel LS;Palmiter RD;Ehrlich I;Lüthi A;Holmes A
适应行为需要为恐惧事件形成记忆，但这些记忆也可以被消除。有效的消退可以防止对感知到的威胁做出过度和持续的反应，这可能发生在焦虑和与创伤和应激源相关的障碍中。然而，尽管有证据表明恐惧的学习和消退是由不同的神经回路介导的，但这些回路之间相互作用的本质仍然知之甚少。在这里，通过体内钙成像、功能操作和切片生理学的结合，我们证明了位于杏仁核的不同的抑制性插入神经元簇(ITCs)在获得和提取恐惧消退记忆的过程中发挥着截然相反的作用。此外，我们发现ITC簇通过相互突触抑制和差异访问功能不同的皮质和中脑投射杏仁核的输出通路而相互拮抗。我们的发现表明，ITC簇之间的活动平衡代表了一个独特的调控基序，该基序协调了一个分布式神经回路，调节高恐惧状态和低恐惧状态之间的切换。这表明，ITCs在杏仁核的一系列功能和相关的大脑状态中发挥着更广泛的作用，这些功能支撑着适应突出环境需求的能力。
Adaptive behaviour necessitates that memories are formed 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’ disorders. However, while there is evidence that fear learning and extinction are mediated by distinct neural circuits, the nature of the interaction between these circuits remains poorly understood. Here, through a combination of in vivo calcium imaging, functional manipulations, and slice physiology, we demonstrate that distinct inhibitory clusters of intercalated neurons (ITCs) located in the amygdala exert diametrically opposite roles during the acquisition and retrieval of fear extinction memory. Furthermore, we find that the ITC clusters antagonize one another via 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 orchestrating a distributed neural circuitry regulating the switch between high and low fear states. This suggests a broader role for the ITCs in a range of amygdala functions and associated brain states underpinning the capacity to adapt to salient environmental demands.
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DOI：
10.1073/pnas.0700293104
发表时间：
2007-03-20
影响因子：
11.1
作者：
Armbruster, Blaine N.;Li, Xiang;Roth, Bryan L.
通讯作者：
Roth, Bryan L.
影响因子：
3
作者：
Arruda-Carvalho M;Clem RL
通讯作者：
Clem RL
影响因子：
16.2
作者：
Duvarci S;Pare D
通讯作者：
Pare D
影响因子：
3.8
作者：
BRAAK, H;BRAAK, E
通讯作者：
BRAAK, E
影响因子：
16.2
作者：
Asede, Douglas;Bosch, Daniel;Ehrlich, Ingrid
通讯作者：
Ehrlich, Ingrid