Fear learning and memory are crucial for animal survival. Abnormal fear memory is a hallmark of many neuropsychiatric disorders. Appropriate neuronal activation and excitability in the basolateral amygdala (BLA) are necessary for the formation of fear memory. The gene cylindromatosis (Cyld), which encodes a lysine-63 deubiquitinase, is expressed in several brain regions including the amygdala. The functions of the cylindromatosis protein (CYLD) in the regulation of the neuronal activity, neural circuits and fear memory, remain largely unknown, however. Here, we report that Cyld knockout impairs amygdala-dependent tone-cued fear memory. The number of c-Fos⁺ neurons responding to the tone-cued fear test was reduced in the BLA of Cyld^–/– mice, suggesting that the absence of CYLD causes aberrant neuronal activation. We found that this aberrant neuronal activation in the BLA of Cyld^–/– mice may relate to the decreased excitability of principal neurons. Another possibility of aberrant neuronal activation could be the impaired excitatory synaptic transmission in the BLA of Cyld^–/– mice. Specifically, both the frequency of spontaneous excitatory postsynaptic currents and the amplitude of miniature excitatory postsynaptic currents in BLA principal neurons were decreased. In addition, Cyld mutation caused an increase in both the frequency of miniature inhibitory postsynaptic currents in principal neurons and the number of parvalbumin⁺ interneurons, consistent with excessive local circuit inhibition in the BLA of Cyld^–/– mice. Taken together, these results suggest that CYLD deficiency disrupts the neuronal activity and synaptic transmission in the BLA of mice which may contribute to the impaired fear memory observed in Cyld^–/– mice.

恐惧学习和记忆对于动物的生存至关重要。异常的恐惧记忆是许多神经精神疾病的标志。基底外侧杏仁核 (BLA) 中适当的神经元激活和兴奋性是形成恐惧记忆所必需的。基因圆柱瘤病 (赛尔德) 编码赖氨酸 63 去泛素化酶，在包括杏仁核在内的几个大脑区域中表达。的职能圆柱瘤病然而，蛋白质（CYLD）在调节神经元活动、神经回路和恐惧记忆中的作用在很大程度上仍然未知。在这里，我们报告说赛尔德敲除会损害依赖杏仁核的音调提示恐惧记忆。在 BLA 中，响应音调提示恐惧测试的 c-Fos ⁺神经元数量减少赛尔德^–/–小鼠，表明 CYLD 的缺失会导致异常的神经元激活。我们发现 BLA 中的这种异常神经元激活赛尔德^–/–小鼠可能与主要神经元的兴奋性降低有关。异常神经元激活的另一种可能性可能是 BLA 中兴奋性突触传递受损赛尔德^–/–老鼠。具体而言，BLA 主要神经元中自发兴奋性突触后电流的频率和微型兴奋性突触后电流的幅度均降低。此外，赛尔德突变导致主要神经元中微型抑制性突触后电流的频率和小清蛋白⁺中间神经元的数量增加，这与 BLA 中过度的局部回路抑制一致赛尔德^–/–老鼠。总之，这些结果表明 CYLD 缺乏破坏了小鼠 BLA 中的神经元活动和突触传递，这可能导致在赛尔德^–/–老鼠。