Guan Zhonghui, Giustetto Maurizio, Lomvardas Stavros, Kim Joung-Hun, Miniaci Maria Concetta, Schwartz James H, Thanos Dimitris, Kandel Eric R
Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USA.
Cell. 2002 Nov 15;111(4):483-93. doi: 10.1016/s0092-8674(02)01074-7.
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.
兴奋性和抑制性输入汇聚于单个神经元，并整合为连贯的输出。尽管我们对短期整合了解颇多，但对于神经元如何对相反信号进行求和以实现长期突触可塑性和记忆存储却知之甚少。在海兔中，我们发现，当一个感觉神经元在一组突触处同时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抑制性递质FMRF酰胺的输入时，长期易化被阻断，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CREB1诱导下游基因C/EBP，CREB1招募CBP进行组蛋白乙酰化，而FMRFa导致CREB2取代CREB1，并招募组蛋白去乙酰化酶5（HDAC5）使组蛋白去乙酰化。当同时应用这两种递质时，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。
