Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien, 970, Taiwan.
Hippocampus. 2013 Jul;23(7):625-33. doi: 10.1002/hipo.22123. Epub 2013 Apr 29.
MicroRNA-132 (miR-132) has been demonstrated to affect multiple neuronal functions, including dendritic growth and spinogenesis in cultured neurons and brain slices, as well as learning behavior of animals. However, its role in acquisition of temporal-associated memory remains unclear. In this study, we demonstrated that the mature miR-132 level in mouse hippocampus was significantly increased at 30 min after trace fear conditioning, a type of temporal-associated learning, and returned to baseline values in 2 h. We then knocked down miR-132 expression in vivo by infusing a lentivector expressing anti-miR-132 hairpin RNA into the third ventricle near the anterior hippocampi such RNA diffused laterally to both hippocampal formations, later confirmed by histological analysis. This approach successfully reduced hippocampal miR-132 expression in both naïve and trace fear conditioned groups, and impaired acquisition of trace fear memory in mice. To our knowledge, this result is the first demonstration of change in temporal learning behavior by reducing microRNA (miRNA) level specifically in the hippocampal region.
MicroRNA-132 (miR-132) 已被证明可影响多种神经元功能，包括培养神经元和脑片中的树突生长和棘突生成，以及动物的学习行为。然而，其在获得时间相关记忆中的作用尚不清楚。在这项研究中，我们证明了在痕迹恐惧条件反射（一种时间相关学习）后 30 分钟，小鼠海马体中的成熟 miR-132 水平显著增加，并在 2 小时后恢复到基线水平。然后，我们通过将表达抗 miR-132 发夹 RNA 的慢病毒注入前海马体附近的第三脑室，在体内敲低 miR-132 的表达，这种 RNA 会侧向扩散到两个海马体，随后通过组织学分析得到证实。这种方法成功地降低了未受训练和痕迹恐惧条件训练组小鼠海马体中的 miR-132 表达，并损害了它们获得痕迹恐惧记忆的能力。据我们所知，这是首次通过特异性降低海马区 miRNA（miRNA）水平来改变时间学习行为的结果。
