PRESYNAPTIC PLASTICITY IN THE AMYGDALA WITH FEAR CONDITIONING

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 恐惧条件反射的巩固涉及大量转录因子和基因的上调。这种转录对于长期记忆的形成是必要的，并受表观遗传调控。染色质修饰在恐惧条件反射和突触可塑性中起着动态作用。在这项研究中，我们发现在体内恐惧条件作用和体外应用BDNF后Hmer 1a mRNA迅速增加，并且这些增加依赖于转录和MAPK信号转导。然后，我们在体内检测了BDNF诱导杏仁核和海马区培养细胞可塑性和恐惧巩固后Hmer 1a启动子的染色质修饰。有趣的是，杏仁核和海马区组织似乎对Homer1a启动子周围的染色质有不同的调节，尽管恐惧条件反射和BDNF诱导的可塑性后mRNA上调相似。这些数据为在BDNF诱导的可塑性之后或在BDNF依赖的学习过程中Hmer 1a的动态调节提供了证据，并且该基因的上调是通过不同的海马区和杏仁体的表观遗传机制来调节的。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The consolidation of fear conditioning involves upregulation of numerous transcription factors and genes. This transcription is necessary for long-term memory formation and is subject to epigenetic regulation. Chromatin modifications play a dynamic role in fear conditioning and synaptic plasticity. In this study, we show that the Homer1a mRNA rapidly increases after fear conditioning in vivo and after BDNF application in vitro and that these increases are dependent on transcription and MAPK signaling. We then examine chromatin modifications of the Homer1a promoter after BDNF-induced plasticity of amygdala and hippocampal cultured cells and after fear consolidation in vivo. Interestingly, amygdala and hippocampal tissues appear to have differential regulation of chromatin around the homer1a promoter despite similar upregulation of mRNA after fear conditioning and BDNF induced plasticity. These data provide evidence for dynamic regulation of Homer1a following BDNF-induced plasticity or during BDNF-dependent learning process, and that upregulation of this gene is regulated through distinct epigenetic mechanisms in the hippocampus and amygdala.