中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (on line): 2-14.doi: 10.4103/NRR.NRR-D-24-00054

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Glutamatergic CYLD deletion leads to aberrant excitatory activity in the basolateral amygdala: association with enhanced cued fear expression

  

  • 出版日期:2024-01-01 发布日期:2024-06-06

Huidong Li1, 2, Faqin Li1, Zhaoyi Chen1, Erwen Wu1, Xiaoxi Dai1, Danni Li1, Haojie An1, Shiyi Zeng1, Chunyan Wang3, Li Yang2, *, Cheng Long1, 4, *   

  1. 1School of Life Sciences, South China Normal University, Guangzhou, Guangdong Province, China; 2School of Life Sciences, Guangzhou University, Guangzhou, Guangdong Province, China; 3Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China; 4South China Normal University-Panyu Central Hospital Joint Laboratory of Translational Medical Research, Panyu Central Hospital, Guangzhou, Guangdong Province, China
  • Online:2024-01-01 Published:2024-06-06
  • Contact: Li Yang, PhD, yang_li@gzhu.edu.cn; Cheng Long, PhD, longcheng@m.scnu.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 32371065 (to CL) and 32170950 (to LY); the Natural Science Foundation of the Guangdong Province, No. 2023A1515010899 (to CL); and the Science and Technology Projects in Guangzhou, Nos. 2023A4J0578 and 2024A03J0180 (to CW).

摘要: https://orcid.org/0000-0001-7448-8588 (Li Yang); https://orcid.org/0000-0002-0904-796X (Cheng Long); https://orcid.org/0009-0008-8069-0166 (Huidong Li)

Abstract: Neuronal activity, synaptic transmission, and molecular changes in the basolateral amygdala play critical roles in fear memory. Cylindromatosis (CYLD) is a deubiquitinase that negatively regulates the nuclear factor kappa-B pathway. CYLD is well studied in non-neuronal cells, yet under-investigated in the brain, where it is highly expressed. Emerging studies have shown involvement of CYLD in the remodeling of glutamatergic synapses, neuroinflammation, fear memory, and anxiety- and autism-like behaviors. However, the precise role of CYLD in glutamatergic neurons is largely unknown. Here, we first proposed involvement of CYLD in cued fear expression. We next constructed transgenic model mice with specific deletion of Cyld from glutamatergic neurons. Our results show that glutamatergic CYLD deficiency exaggerated the expression of cued fear in only male mice. Further, loss of CYLD in glutamatergic neurons resulted in enhanced neuronal activation, impaired excitatory synaptic transmission, and altered levels of glutamate receptors accompanied by over-activation of microglia in the basolateral amygdala of male mice. Altogether, our study suggests a critical role of glutamatergic CYLD in maintaining normal neuronal, synaptic, and microglial activation. This may contribute, at least in part, to cued fear expression.

Key words: basolateral amygdala, cued fear expression, cylindromatosis, deubiquitinase, glutamate receptor 1, glutamatergic neuron, microglial activation, N-methyl-D-aspartate receptor 1, neuronal activation, synaptic transmission