Deficiency of the CYLD Impairs Fear Memory of Mice and Disrupts Neuronal Activity and Synaptic Transmission in the Basolateral Amygdala.
Deficiency of the CYLD Impairs Fear Memory of Mice and Disrupts Neuronal Activity and Synaptic Transmission in the Basolateral Amygdala.
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CYLD 缺陷会损害小鼠的恐惧记忆并扰乱基底外侧杏仁核的神经元活动和突触传递
DOI：
10.3389/fncel.2021.740165
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发表时间：
2021
影响因子：
5.3
通讯作者：
Long C
中科院分区：
文献类型：
--
作者：
Li HD;Li DN;Yang L;Long C
恐惧学习和记忆对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。在基底外侧杏仁核（BLA）中适当的神经元激活和兴奋性是恐惧记忆形成的必要条件。基因柱状瘤病（Cyld）编码赖氨酸-63去泛素酶，在包括杏仁核在内的几个大脑区域表达。然而，圆柱形瘤病蛋白（CYLD）在调节神经元活动、神经回路和恐惧记忆中的功能在很大程度上仍然未知。在这里，我们报道Cyld敲除会损害杏仁核依赖的音调提示的恐惧记忆。Cyld - / -小鼠BLA中对音调提示恐惧测试有反应的c-Fos+神经元数量减少，提示Cyld缺失导致神经元异常激活。我们发现Cyld - / -小鼠BLA中这种异常的神经元激活可能与主要神经元兴奋性降低有关。另一种异常神经元激活的可能性可能是Cyld - / -小鼠BLA的兴奋性突触传递受损。具体而言，BLA主神经元自发兴奋性突触后电流频率和微型兴奋性突触后电流幅度均降低。此外，Cyld突变导致主神经元突触后微型抑制性电流频率和小白蛋白+中间神经元数量增加，与Cyld - / -小鼠BLA局部电路过度抑制一致。综上所述，这些结果表明，CYLD缺乏破坏了小鼠BLA的神经元活动和突触传递，这可能是CYLD - / -小鼠恐惧记忆受损的原因。
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.
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