Cerebellar interneurons control fear memory consolidation via learning-induced HCN plasticity.
Cerebellar interneurons control fear memory consolidation via learning-induced HCN plasticity.
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小脑中神经元通过学习引起的HCN可塑性来控制恐惧记忆巩固。
DOI：
10.1016/j.celrep.2023.113057
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发表时间：
2023-09-26
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
虽然突触可塑性被认为是学习和记忆的基础，但神经元内在兴奋性的改变可以放大神经元回路的输出，从而改变行为。然而，在记忆形成过程中，学习诱导的内在兴奋性变化的机制还知之甚少。在小脑中，我们发现沉默分子层中间神经元完全消除了恐惧记忆，揭示了它们在记忆巩固中的关键作用。恐惧条件反射范式在这些中间神经元中产生超极化激活的环核苷酸门控（HCN）通道的持久减少。这种变化增加了内在的膜兴奋性，并增强了对突触刺激的反应。HCN损失是由内源性大麻素水平的降低通过改变cGMP信号传导驱动的。相反，在记忆巩固过程中，小脑内源性大麻素释放的增加会消除HCN的可塑性。因此，小脑中间神经元的活动通过内在兴奋性的学习特异性增加来驱动恐惧记忆的形成，而这个过程需要内源性大麻素-HCN信号的丧失。Carzoli等人揭示，小脑中间神经元的活动通过内在兴奋性的学习特异性增加来驱动恐惧记忆的形成，而这一过程需要内源性大麻素-HCN信号的丧失。这突出了超越传统的以突触可塑性为重点的记忆形成研究的重要性。
While synaptic plasticity is considered the basis of learning and memory, modifications of the intrinsic excitability of neurons can amplify the output of neuronal circuits and consequently change behavior. However, the mechanisms that underlie learning-induced changes in intrinsic excitability during memory formation are poorly understood. In the cerebellum, we find that silencing molecular layer interneurons completely abolishes fear memory, revealing their critical role in memory consolidation. The fear conditioning paradigm produces a lasting reduction in hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in these interneurons. This change increases intrinsic membrane excitability and enhances the response to synaptic stimuli. HCN loss is driven by a decrease in endocannabinoid levels via altered cGMP signaling. In contrast, an increase in release of cerebellar endocannabinoids during memory consolidation abolishes HCN plasticity. Thus, activity in cerebellar interneurons drives fear memory formation via a learning-specific increase in intrinsic excitability, and this process requires the loss of endocannabinoid-HCN signaling. Carzoli et al. reveal that activity in cerebellar interneurons drives fear memory formation via a learning-specific increase in intrinsic excitability, and this process requires the loss of endocannabinoid-HCN signaling. This highlights the importance of moving beyond traditional synaptic plasticity-focused investigations of memory formation.
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影响因子：
16.2
作者：
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通讯作者：
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影响因子：
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抑制性神经传递驱动内源性大麻素降解以促进记忆巩固。
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DOI：
10.1016/j.bbrc.2003.09.197
发表时间：
2003-11-07
影响因子：
3.1
作者：
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通讯作者：
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影响因子：
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作者：
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