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蓝斑通过协调恐惧记忆与感觉输入的有效整合来影响行为。

The locus coeruleus influences behavior by coordinating effective integration of fear memories and sensory input.

作者信息

Duan Haoyu, Wang Tianyu, Zhang Xinyang, Xia Dan, Wang Zeyi, Fong Tsz Hei, Li Tianxiang, Yan Rongzhen, Zhan Yang, Li Yulong, Gao Wen-Jun, Zhou Qiang

机构信息

State Key Laboratory of Chemical Oncogenomics, Guangdong Provincial Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China.

Cellular and Molecular Diagnostics Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

出版信息

PLoS Biol. 2025 Jul 14;23(7):e3003272. doi: 10.1371/journal.pbio.3003272. eCollection 2025 Jul.

Abstract

An essential function of memory is to guide behavior for better survival and adaptation. While memory formation has been extensively studied, far less is understood about how memory retrieval influences behaviors. In the auditory Pavlovian threat conditioning paradigm using C57BL/6J mice, retrieving a conditioned threat memory is associated with spiking in two dorsomedial prefrontal cortex (dmPFC) neurons with transient (T-neurons) and sustained (S-neurons) patterns. We show here that T-neurons and S-neurons are two distinct neuronal populations with different neuronal and synaptic properties and mRNA profiles. S-neuron spiking matches freezing behavior and is required for freezing. This sustained activity in S-neurons requires auditory inputs and the release of norepinephrine (NE) in the dmPFC. The activation of the locus coeruleus (LC) is initiated by dmPFC T-neuron inputs, sustained by auditory inputs, and is required for the transition to freezing by enhancing S-neuron activity. Interestingly, LC activation precipitates a brief period during which nonconditioned cues also induce freezing. Our findings highlight the critical contribution of the LC/NE system in the transition from memory to behavior, which coordinates the effective integration of memory, sensory inputs and emotional state for optimal adaptation.

摘要

记忆的一项基本功能是引导行为,以实现更好的生存和适应。虽然记忆形成已得到广泛研究,但对于记忆提取如何影响行为的了解却少得多。在使用C57BL/6J小鼠的听觉巴甫洛夫式威胁条件反射范式中,提取条件性威胁记忆与两个背内侧前额叶皮层(dmPFC)神经元的放电有关,其放电模式为瞬态(T神经元)和持续(S神经元)。我们在此表明,T神经元和S神经元是两个不同的神经元群体,具有不同的神经元和突触特性以及mRNA谱。S神经元放电与僵住行为匹配,且是僵住所必需的。S神经元中的这种持续活动需要听觉输入以及dmPFC中去甲肾上腺素(NE)的释放。蓝斑(LC)的激活由dmPFC T神经元输入启动,并由听觉输入维持,且通过增强S神经元活动来实现向僵住的转变。有趣的是,LC激活会引发一个短暂时期,在此期间非条件性线索也会诱发僵住。我们的研究结果突出了LC/NE系统在从记忆到行为转变中的关键作用,该系统协调记忆、感觉输入和情绪状态的有效整合以实现最佳适应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/405b/12273993/879003267fc6/pbio.3003272.g002.jpg

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