Altered cortical synaptic morphology and impaired memory consolidation in forebrain-specific dominant- negative PAK transgenic mice
Altered cortical synaptic morphology and impaired memory consolidation in forebrain-specific dominant- negative PAK transgenic mice
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DOI：
10.1016/j.neuron.2004.05.003
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发表时间：
2004-06-10
期刊：
影响因子：
16.2
通讯作者：
Tonegawa, S
中科院分区：
文献类型：
--
作者：
Hayashi, ML;Choi, SY;Tonegawa, S
大脑皮层中记忆巩固的分子和细胞机制知之甚少。为了研究皮层突触结构和功能与长期记忆巩固之间的关系，我们产生了转基因小鼠，其中PAK的催化活性，肌动蛋白重塑的关键调节剂，在出生后前脑中被抑制。与野生型对照组相比，这些小鼠的皮质神经元显示出较少的树突棘和较大突触的比例增加。基础突触形态的这些改变与皮质中平均突触强度增强和双向突触可修饰性受损（LTP增强和LTD减少）相关。相比之下，这些小鼠的海马中的脊柱形态和突触可塑性是正常的。重要的是，这些小鼠表现出特定的缺陷，在巩固阶段的海马依赖性记忆。因此，我们的研究结果提供了证据，突触形态和双向修改的突触强度在皮层和长期记忆的巩固之间的关键关系。
Molecular and cellular mechanisms for memory consolidation in the cortex are poorly known. To study the relationships between synaptic structure and function in the cortex and consolidation of long-term memory, we have generated transgenic mice in which catalytic activity of PAK, a critical regulator of actin remodeling, is inhibited in the postnatal forebrain. Cortical neurons in these mice displayed fewer dendritic spines and an increased proportion of larger synapses compared to wild-type controls. These alterations in basal synaptic morphology correlated with enhanced mean synaptic strength and impaired bidirectional synaptic modifiability (enhanced LTP and reduced LTD) in the cortex. By contrast, spine morphology and synaptic plasticity were normal in the hippocampus of these mice. Importantly, these mice exhibited specific deficits in the consolidation phase of hippocampus-dependent memory. Thus, our results provide evidence for critical relationships between synaptic morphology and bidirectional modifiability of synaptic strength in the cortex and consolidation of long-term memory.