Lattal K Matthew, Barrett Ruth M, Wood Marcelo A
Department of Behavioral Neuroscience, Oregon Health & Science University, OR 97239-3098, USA.
Behav Neurosci. 2007 Oct;121(5):1125-31. doi: 10.1037/0735-7044.121.5.1125.
Several recent studies have shown that chromatin, the DNA-protein complex that packages genomic DNA, has an important function in learning and memory. Dynamic chromatin modification via histone deacetylase (HDAC) inhibitors and histone acetyltransferases may enhance hippocampal synaptic plasticity and hippocampus-dependent memory. Little is known about the effects of HDAC inhibitors on extinction, a learning process through which the ability of a previously conditioned stimulus, such as a conditioning context, to evoke a conditioned response is diminished. The authors demonstrate that administration of the HDAC inhibitors sodium butyrate (NaB) systemically or trichostatin A (TSA) intrahippocampally prior to a brief (3-min) contextual extinction session causes context-evoked fear to decrease to levels observed with a long (24-min) extinction session. These results suggest that HDAC inhibitors may enhance learning during extinction and are consistent with other studies demonstrating a role for the hippocampus in contextual extinction. Molecular and behavioral mechanisms through which this enhanced extinction effect may occur are discussed.
最近的几项研究表明，染色质，即包装基因组DNA的DNA-蛋白质复合物，在学习和记忆中具有重要功能。通过组蛋白去乙酰化酶（HDAC）抑制剂和组蛋白乙酰转移酶进行的动态染色质修饰可能会增强海马体突触可塑性和海马体依赖性记忆。关于HDAC抑制剂对消退的影响知之甚少，消退是一个学习过程，通过这个过程，先前条件刺激（如条件化情境）诱发条件反应的能力会减弱。作者证明，在短暂（3分钟）的情境消退训练之前，全身给予HDAC抑制剂丁酸钠（NaB）或海马体内给予曲古抑菌素A（TSA），会使情境诱发的恐惧降低到与长时间（24分钟）消退训练所观察到的水平。这些结果表明，HDAC抑制剂可能会增强消退过程中的学习，并且与其他证明海马体在情境消退中起作用的研究一致。本文讨论了这种增强的消退效应可能发生的分子和行为机制。
