α3-Integrins are required for hippocampal long-term potentiation and working memory
α3-Integrins are required for hippocampal long-term potentiation and working memory
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DOI：
10.1101/lm.648607
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发表时间：
2007-09-01
影响因子：
2
通讯作者：
Davis, Ronald L.
中科院分区：
文献类型：
--
作者：
Chan, Chi-Shing;Levenson, Jonathan M.;Davis, Ronald L.
整合素是一个异源二聚体跨膜细胞黏附受体大家族，在发育中和成人中枢神经系统中介导不同的神经功能。最近的药理学和遗传学研究表明，β1整合素在突触可塑性和记忆形成中起关键作用。为了进一步确定整合素在这些过程中的作用，我们产生了出生后前脑和兴奋性神经元特异性的α3-整合素敲除，α3-整合素是β1亚单位的几个结合伙伴之一。在海马Schaffer侧支-CA1突触，α3整合素的缺失导致长时程增强(LTP)受损。在缺乏α3整合素的情况下，基础突触传递和成对脉冲易化是正常的。行为学研究表明，突变小鼠在依赖于海马体的、不匹配到地点的工作记忆任务中存在选择性缺陷，但在其他依赖于海马体的空间任务中是正常的。LTP和工作记忆的损害与在α1-整合素条件基因敲除小鼠中观察到的相似，表明α3-整合素是前脑这些过程中β1的功能结合伙伴。
Integrins comprise a large family of heterodimeric, transmembrane cell adhesion receptors that mediate diverse neuronal functions in the developing and adult CNS. Recent pharmacological and genetic studies have suggested that beta 1-integrins are critical in synaptic plasticity and memory formation. To further define the role of integrins in these processes, we generated a postnatal forebrain and excitatory neuron-specific knockout of alpha 3-integrin, one of several binding partners for beta 1 subunit. At hippocampal Schaffer collateral-CA1 synapses, deletion of alpha 3-integrin resulted in impaired long-term potentiation (LTP). Basal synaptic transmission and paired-pulse facilitation were normal in the absence of alpha 3-integrin. Behavioral studies demonstrated that the mutant mice were selectively defective in a hippocampus-dependent, nonmatch-to-place working memory task, but were normal in other hippocampus-dependent spatial tasks. The impairment in LTP and working memory is similar to that observed in alpha 1-integrin conditional knockout mice, suggesting that alpha 3-integrin is the functional binding partner for beta 1 for these processes in the forebrain.