Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetylation
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Animals
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Aplysia
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CCAAT-Enhancer-Binding Proteins / genetics*
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CCAAT-Enhancer-Binding Proteins / metabolism
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CREB-Binding Protein
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Chromatin / physiology*
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Cyclic AMP Response Element-Binding Protein
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FMRFamide / pharmacology
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Gene Expression Regulation*
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Histone Deacetylases / genetics*
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Histones / genetics
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Long-Term Potentiation / physiology*
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Long-Term Synaptic Depression / physiology*
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Motor Neurons / drug effects
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Motor Neurons / physiology
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Nerve Tissue Proteins / genetics*
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Nerve Tissue Proteins / metabolism
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Neurons, Afferent / drug effects
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Neurons, Afferent / physiology
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Nuclear Proteins / genetics*
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Nuclear Proteins / metabolism
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Repressor Proteins / genetics*
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Repressor Proteins / metabolism
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Serotonin / pharmacology
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Synapses
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TATA-Box Binding Protein / genetics
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TATA-Box Binding Protein / metabolism
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Trans-Activators / genetics*
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Trans-Activators / metabolism
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Transcription Factors / genetics*
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Transcription Factors / metabolism
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Transcription, Genetic
Substances
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ApCREB2 protein, Aplysia californica
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CCAAT-Enhancer-Binding Proteins
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Chromatin
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Cyclic AMP Response Element-Binding Protein
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Histones
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Nerve Tissue Proteins
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Nuclear Proteins
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Repressor Proteins
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TATA-Box Binding Protein
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Trans-Activators
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Transcription Factors
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Serotonin
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FMRFamide
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CREB-Binding Protein
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Histone Deacetylases