Integration of long-term-memory-related synaptic plasticity involves bidirectional regulation of gene expression and chromatin structure
Integration of long-term-memory-related synaptic plasticity involves bidirectional regulation of gene expression and chromatin structure
复制标题
DOI：
10.1016/s0092-8674(02)01074-7
复制
发表时间：
2002-11-15
期刊：
影响因子：
64.5
通讯作者：
Kandel, ER
中科院分区：
文献类型：
--
作者：
Guan, ZH;Giustetto, M;Kandel, ER
兴奋性和抑制性输入汇聚于单个神经元，并整合为一个连贯的输出。尽管对短期整合已有很多了解，但对于神经元如何对长期突触可塑性和记忆存储的相反信号进行求和却知之甚少。在海兔中，我们发现当一个感觉神经元同时在一组突触处接收来自易化性递质5 - 羟色胺（5 - HT）的输入，而在另一组突触处接收来自抑制性递质FMRFamide的输入时，长期易化被阻断，且突触特异性的长期抑制占主导。染色质免疫沉淀分析表明，5 - HT通过激活环磷腺苷效应元件结合蛋白1（CREB1）诱导下游基因C/EBP，CREB1招募CREB结合蛋白（CBP）进行组蛋白乙酰化，而FMRFa导致CREB1被CREB2取代，并招募组蛋白去乙酰化酶5（HDAC5）使组蛋白去乙酰化。当这两种递质同时施加时，易化被阻断，因为CREB2和HDAC5取代了CREB1 - CBP，从而使组蛋白去乙酰化。
Excitatory and inhibitory inputs converge on single neurons and are integrated into a coherent output. Although much is known about short-term integration, little is known about how neurons sum opposing signals for long-term synaptic plasticity and memory storage. In Aplysia, we find that when a sensory neuron simultaneously receives inputs from the facilitatory transmitter 5-HT at one set of synapses and the inhibitory transmitter FMRFamide at another, long-term facilitation is blocked and synapse-specific long-term depression dominates. Chromatin immunoprecipitation assays show that 5-HT induces the downstream gene C/EBP by activating CREB1, which recruits CBP for histone acetylation, whereas FMRFa leads to CREB1 displacement by CREB2 and recruitment of HDAC5 to deacetylate histones. When the two transmitters are applied together, facilitation is blocked because CREB2 and HDAC5 displace CREB1-CBP, thereby deacetylating histones.