IMPAIRED LONG-TERM POTENTIATION, SPATIAL-LEARNING, AND HIPPOCAMPAL DEVELOPMENT IN FYN MUTANT MICE
IMPAIRED LONG-TERM POTENTIATION, SPATIAL-LEARNING, AND HIPPOCAMPAL DEVELOPMENT IN FYN MUTANT MICE
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DOI：
10.1126/science.1361685
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发表时间：
1992-12-18
期刊：
影响因子：
56.9
通讯作者：
KANDEL, ER
中科院分区：
文献类型：
--
作者：
GRANT, SGN;ODELL, TJ;KANDEL, ER
本研究采用四种非受体酪氨酸激酶基因fyn、src、yes和abl突变的小鼠，研究这些激酶在长时程增强（LTP）中的作用以及LTP与空间学习记忆的关系。所有四种激酶都在海马中表达。src、yes和abl的突变不干扰LTP的诱导或维持。然而，在fyn突变体，LTP钝化，即使突触传递和两个短期形式的突触可塑性，成对脉冲促进和强直后增强，是正常的。与LTP的钝化平行，fyn突变体表现出受损的空间学习，与LTP和学习之间的功能联系一致。虽然fyn在成熟的突触中表达，但其在发育过程中缺乏表达导致齿状回中颗粒细胞和CA3区域中锥体细胞数量增加。因此，一个共同的酪氨酸激酶途径可以调节发育中的海马神经元的生长和成熟海马突触可塑性的强度。
Mice with mutations in four nonreceptor tyrosine kinase genes, fyn, src, yes, and abl, were used to study the role of these kinases in long-term potentiation (LTP) and in the relation of LTP to spatial learning and memory. All four kinases were expressed in the hippocampus. Mutations in src, yes, and abl did not interfere with either the induction or the maintenance of LTP. However, in fyn mutants, LTP was blunted even though synaptic transmission and two short-term forms of synaptic plasticity, paired-pulse facilitation and post-tetanic potentiation, were normal. In parallel with the blunting of LTP, fyn mutants showed impaired spatial learning, consistent with a functional link between LTP and learning. Although fyn is expressed at mature synapses, its lack of expression during development resulted in an increased number of granule cells in the dentate gyrus and of pyramidal cells in the CA3 region. Thus, a common tyrosine kinase pathway may regulate the growth of neurons in the developing hippocampus and the strength of synaptic plasticity in the mature hippocampus.