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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Inflammation
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1412699
This article is part of the Research Topic Remedying the injured brain in cognitive impairment: potential neuroimmune communication signaling and therapeutic opportunities View all articles

The microglial innate immune receptor TREM2 participates in fear memory formation through excessive prelimbic cortical synaptic pruning

Provisionally accepted
Lele Zhang Lele Zhang 1Peng Cheng Peng Cheng 2Yuan-Qing Chu Yuan-Qing Chu 2Zi-Ming Zhou Zi-Ming Zhou 2Rong Hua Rong Hua 3*Yong-mei Zhang Yong-mei Zhang 2*
  • 1 Other
  • 2 Xuzhou Medical University, Xuzhou, Jiangsu Province, China
  • 3 Department of Emergency, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China, Xuzhou, China

The final, formatted version of the article will be published soon.

    Fear memory formation has been implicated in fear-and stress-related psychiatric disorders, including post-traumatic stress disorder (PTSD) and phobias. Synapse deficiency and microglial activation are common among patients with PTSD, and induced in animal models of fear conditioning. Increasing studies now focus on explaining the specific mechanisms between microglia and synapse deficiency. Though newly-identified microglia regulator triggering receptor expressed on myeloid cells 2 (TREM2) plays a role in microglial phagocytic activity, its role in fear-formation remains unknown. The results herein indicate that the foot-shock protocol in male mice resulted in a fear formation model. Mechanistically, fear conditioning enhanced the microglial capacity for engulfing synapse materials, and led to glutamatergic neuron activation in the prelimbic cortex. Prelimbic chemical deletion or microglia inhibition improved fear memory formation. Further investigation demonstrated that TREM2 regulates microglial phagocytosis, enhancing synaptic pruning. Trem2 knockout mice showed remarkable reductions in prelimbic synaptic pruning and reduced neuron activation, with decreased fear memory formation. Our cumulative results suggest that prelimbic TREM2-mediated excessive microglial synaptic pruning is involved in the fear memory formation process, leading to development of abnormal stress-related behavior.

    Keywords: fear memory formation, prelimbic, Microglia, synaptic pruning, TREM2

    Received: 05 Apr 2024; Accepted: 14 Oct 2024.

    Copyright: © 2024 Zhang, Cheng, Chu, Zhou, Hua and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Rong Hua, Department of Emergency, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China, Xuzhou, China
    Yong-mei Zhang, Xuzhou Medical University, Xuzhou, 221004, Jiangsu Province, China

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