Myristoylated alanine rich C kinase substrate (MARCKS) heterozygous mutant mice exhibit deficits in hippocampal mossy fiber-CA3 long-term potentiation
Myristoylated alanine rich C kinase substrate (MARCKS) heterozygous mutant mice exhibit deficits in hippocampal mossy fiber-CA3 long-term potentiation
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DOI：
10.1002/hipo.20177
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发表时间：
2006-01-01
期刊：
影响因子：
3.5
通讯作者：
McNamara, RK
中科院分区：
文献类型：
--
作者：
Hussain, RJ;Sturnpo, DJ;McNamara, RK
富含豆蔻酰丙氨酸的C激酶底物（MARCKS）是脑中主要的蛋白激酶C（PKC）底物，被认为将PKC信号传导到丝状（F）肌动蛋白细胞骨架的改变中。在成年海马中，MARCKS在齿状回（DG）-CA 3苔藓纤维通路中高度表达，但在CA 3-CA 1-Schaffer侧支-CA 1通路中以低水平表达。我们以前已经证明，在杂合子Marcks突变小鼠中，MARCKS表达减少50%会在空间反转学习中产生强烈的缺陷，但不会产生背景恐惧条件反射，这表明只有海马功能的特定方面受到MARCKS表达减少的损害。为了进一步阐明MARCKS在海马突触可塑性中的作用，在本研究中，我们研究了基础突触传递，成对脉冲易化，强直后增强，和长时程增强（LTP）在海马苔藓纤维CA 3和Schaffer侧支CA 1通路的杂合子MARCKS突变和野生型小鼠。我们发现，LTP是显着受损的苔藓纤维-CA 3通路，但不是在谢弗侧支-CA 1通路，在杂合子的Marcks突变小鼠，而基础突触传递，成对脉冲促进，和强直后增强不受影响的两个途径。这些发现表明，MARCKS表达减少50%会损害苔藓纤维-CA 3通路中长期而非短期突触可塑性所需的过程。这些发现的苔藓纤维CA 3通路的作用，在依赖于学习过程中的影响进行了讨论。(c)2006 Wiley-Liss Inc.
The myristoylated alanine-rich C kinase substrate (MARCKS) is a primary protein kinase C (PKC) substrate in brain thought to transduce PKC signaling into alterations in the filamentous (F) actin cytoskeleton. Within the adult hippocampus, MARCKS is highly expressed in the dentate gyrus (DG)-CA3 mossy fiber pathway, but is expressed at low levels in the CA3-CA1 Schaffer collateral-CA1 pathway. We have previously demonstrated that 50% reductions in MARCKS expression in heterozygous Marcks mutant mice produce robust deficits in spatial reversal learning, but not contextual fear conditioning, suggesting that only specific aspects of hippocampal function are impaired by reduction in MARCKS expression. To further elucidate the role of MARCKS in hippocampal synaptic plasticity, in the present study we examined basal synaptic transmission, paired-pulse facilitation, post-tetanic potentiation, and long-term potentiation (LTP) in the hippocampal mossy fiber-CA3 and Schaffer collateral-CA1 pathways of heterozygous Marcks mutant and wild-type mice. We found that LTP is significantly impaired in the mossy fiber-CA3 pathway, but not in the Schaffer collateral-CA1 pathway, in heterozygous Marcks mutant mice, whereas basal synaptic transmission, paired-pulse facilitation, and post-tetanic potentiation are unaffected in both pathways. These findings indicate that a 50% reduction in MARCKS expression impairs processes required for long-term, but not short-term synaptic plasticity in the mossy fiber-CA3 pathway. The implications of these findings for the role of the mossy fiber-CA3 pathway in hippocampus-dependent learning processes are discussed. (c) 2006 Wiley-Liss Inc.