HDAC inhibition modulates hippocampus-dependent long-term memory for object location in a CBP-dependent manner
HDAC inhibition modulates hippocampus-dependent long-term memory for object location in a CBP-dependent manner
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DOI：
10.1101/lm.1986911
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发表时间：
2011-02-01
影响因子：
2
通讯作者：
Wood, Marcelo A.
中科院分区：
文献类型：
--
作者：
Haettig, Jakob;Stefanko, Daniel P.;Wood, Marcelo A.
长期记忆所需基因的转录不仅涉及转录因子，还涉及改变染色质结构的酶蛋白复合物。染色质修饰酶，如组蛋白乙酰转移酶（HAT）CREB（环AMP反应元件结合）结合蛋白（CBP），是长期记忆所需的转录调控的关键。一些研究表明，CBP和组蛋白乙酰化是海马依赖性长时程记忆和海马长时程增强（LTP）所必需的。重要的是，每一个转基因的Cbp突变小鼠在物体识别方面都表现出长期记忆障碍。然而，海马体在物体识别中的作用是有争议的。为了更好地理解染色质修饰酶如何调节物体识别的长期记忆，我们首先研究了海马在物体识别或物体定位的长期记忆检索中的作用。蝇蕈醇失活的背侧海马检索前对物体识别的长期记忆没有影响，但完全阻断长期记忆的对象位置。这与海马蝇蕈醇失活对物体本身的长期记忆没有影响的实验相一致，支持海马编码关于物体的空间信息（如位置或背景），而皮层区域（如嗅周或岛叶皮层）编码关于物体本身的信息。使用位置依赖的对象识别任务，从事海马，我们表明，CBP是必不可少的长期记忆的调制通过HDAC抑制。总之，这些结果表明HDAC抑制通过CBP调节海马中的记忆，并且不同的脑区域利用不同的染色质修饰酶来调节学习和记忆。
Transcription of genes required for long-term memory not only involves transcription factors, but also enzymatic protein complexes that modify chromatin structure. Chromatin-modifying enzymes, such as the histone acetyltransferase (HAT) CREB (cyclic-AMP response element binding) binding protein (CBP), are pivotal for the transcriptional regulation required for long-term memory. Several studies have shown that CBP and histone acetylation are necessary for hippocampus-dependent long-term memory and hippocampal long-term potentiation (LTP). Importantly, every genetically modified Cbp mutant mouse exhibits long-term memory impairments in object recognition. However, the role of the hippocampus in object recognition is controversial. To better understand how chromatin-modifying enzymes modulate long-term memory for object recognition, we first examined the role of the hippocampus in retrieval of long-term memory for object recognition or object location. Muscimol inactivation of the dorsal hippocampus prior to retrieval had no effect on long-term memory for object recognition, but completely blocked long-term memory for object location. This was consistent with experiments showing that muscimol inactivation of the hippocampus had no effect on long-term memory for the object itself, supporting the idea that the hippocampus encodes spatial information about an object (such as location or context), whereas cortical areas (such as the perirhinal or insular cortex) encode information about the object itself. Using location-dependent object recognition tasks that engage the hippocampus, we demonstrate that CBP is essential for the modulation of long-term memory via HDAC inhibition. Together, these results indicate that HDAC inhibition modulates memory in the hippocampus via CBP and that different brain regions utilize different chromatin-modifying enzymes to regulate learning and memory.