Hu Jiang-Yuan, Levine Amir, Sung Ying-Ju, Schacher Samuel
Department of Neuroscience, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, New York, New York 10032 and
Department of Neuroscience, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, New York, New York 10032 and.
J Neurosci. 2015 Jan 7;35(1):386-95. doi: 10.1523/JNEUROSCI.3284-14.2015.
Basic region leucine zipper (bZIP) transcription factors regulate gene expression critical for long-term synaptic plasticity or neuronal excitability contributing to learning and memory. At sensorimotor synapses of Aplysia, changes in activation or expression of CREB1 and CREB2 in sensory neurons are required for long-term synaptic plasticity. However, it is unknown whether concomitant stimulus-induced changes in expression and activation of bZIP transcription factors in the postsynaptic motor neuron also contribute to persistent long-term facilitation (P-LTF). We overexpressed various forms of CREB1, CREB2, or cJun in the postsynaptic motor neuron L7 in cell culture to examine whether these factors contribute to P-LTF. P-LTF is evoked by 2 consecutive days of 5-HT applications (2 5-HT), while a transient form of LTF is produced by 1 day of 5-HT applications (1 5-HT). Significant increases in the expression of both cJun and CREB2 mRNA in L7 accompany P-LTF. Overexpressing each bZIP factor in L7 did not alter basal synapse strength, while coexpressing cJun and CREB2 in L7 evoked persistent increases in basal synapse strength. In contrast, overexpressing cJun and CREB2 in sensory neurons evoked persistent decreases in basal synapse strength. Overexpressing wild-type cJun or CREB2, but not CREB1, in L7 can replace the second day of 5-HT applications in producing P-LTF. Reducing cJun activity in L7 blocked P-LTF evoked by 2 5-HT. These results suggest that expression and activation of different bZIP factors in both presynaptic and postsynaptic neurons contribute to persistent change in synapse strength including stimulus-dependent long-term synaptic plasticity.
碱性区域亮氨酸拉链(bZIP)转录因子调节对长期突触可塑性或神经元兴奋性至关重要的基因表达,而长期突触可塑性和神经元兴奋性有助于学习和记忆。在海兔的感觉运动突触中,感觉神经元中CREB1和CREB2的激活或表达变化是长期突触可塑性所必需的。然而,尚不清楚突触后运动神经元中bZIP转录因子伴随刺激诱导的表达和激活变化是否也有助于持续性长期易化(P-LTF)。我们在细胞培养中过表达突触后运动神经元L7中的各种形式的CREB1、CREB2或cJun,以检查这些因子是否有助于P-LTF。P-LTF由连续2天应用5-羟色胺(2次5-羟色胺)诱发,而短暂形式的LTF由1天应用5-羟色胺(1次5-羟色胺)产生。L7中cJun和CREB2 mRNA的表达均伴随P-LTF显著增加。在L7中过表达每个bZIP因子不会改变基础突触强度,而在L7中共表达cJun和CREB2会诱发基础突触强度持续增加。相反,在感觉神经元中过表达cJun和CREB2会诱发基础突触强度持续降低。在L7中过表达野生型cJun或CREB2而非CREB1,可以替代5-羟色胺应用的第二天来产生P-LTF。降低L7中的cJun活性会阻断由2次5-羟色胺诱发的P-LTF。这些结果表明,突触前和突触后神经元中不同bZIP因子的表达和激活有助于突触强度的持续变化,包括依赖刺激的长期突触可塑性。