小GTP酶Rac1在海马可塑性以及空间学习与记忆中起核心作用。
A central role for the small GTPase Rac1 in hippocampal plasticity and spatial learning and memory.
作者信息
Haditsch Ursula, Leone Dino P, Farinelli Mélissa, Chrostek-Grashoff Anna, Brakebusch Cord, Mansuy Isabelle M, McConnell Susan K, Palmer Theo D
机构信息
Department of Neurosurgery, Stanford School of Medicine, 1201 Welch Rd, MSLS P304, Stanford, California 94305, USA.
出版信息
Mol Cell Neurosci. 2009 Aug;41(4):409-19. doi: 10.1016/j.mcn.2009.04.005. Epub 2009 Apr 24.
Abstract
Rac1 is a member of the Rho family of small GTPases that are important for structural aspects of the mature neuronal synapse including basal spine density and shape, activity-dependent spine enlargement, and AMPA receptor clustering in vitro. Here we demonstrate that selective elimination of Rac1 in excitatory neurons in the forebrain in vivo not only affects spine structure, but also impairs synaptic plasticity in the hippocampus with consequent defects in hippocampus-dependent spatial learning. Furthermore, Rac1 mutants display deficits in working/episodic-like memory in the delayed matching-to-place (DMP) task suggesting that Rac1 is a central regulator of rapid encoding of novel spatial information in vivo.
摘要
Rac1是小GTP酶Rho家族的成员，对成熟神经元突触的结构方面很重要，包括基底棘密度和形状、活动依赖性棘增大以及体外AMPA受体聚集。在这里，我们证明，体内选择性消除前脑兴奋性神经元中的Rac1不仅会影响棘突结构，还会损害海马体中的突触可塑性，进而导致海马体依赖性空间学习出现缺陷。此外，Rac1突变体在延迟位置匹配（DMP）任务中的工作/情景样记忆存在缺陷，这表明Rac1是体内新空间信息快速编码的核心调节因子。
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