Impaired spatial learning and defective theta burst induced LTP in mice lacking fibroblast growth factor 14
Impaired spatial learning and defective theta burst induced LTP in mice lacking fibroblast growth factor 14
复制标题
DOI：
10.1016/j.nbd.2006.11.014
复制
发表时间：
2007-04-01
影响因子：
6.1
通讯作者：
Ornitz, David M.
中科院分区：
文献类型：
--
作者：
Wozniak, David F.;Xiao, Maolei;Ornitz, David M.
脊髓小脑性共济失调 27 (SCA27) 是最近描述的一种综合征，其特征是认知能力受损和缓慢进行性共济失调。 SCA27 是由成纤维细胞生长因子 14 (FGF14) 的常染色体显性错义突变引起的。缺乏FGF14的小鼠（Fgf14(-/-)小鼠）感觉运动功能受损、共济失调和阵发性运动障碍，这种表型导致了人类突变的发现。在这里，我们通过证明 Fgf14(-/-) 小鼠在莫里斯水迷宫中表现出可靠的习得（位置学习）缺陷，扩展了 Fgf14(-/-) 小鼠和 FGF14(F145S) 人类之间的相似性。这种认知缺陷似乎与感觉运动障碍无关，并且具有相对选择性，因为 Fgf14(-/-) 小鼠在提示水迷宫试验以及条件恐惧和被动回避测试中与野生型同窝小鼠表现相似。在 Fgf14(-/-) 小鼠的海马切片中也发现了受损的 theta 爆发引发的长期突触增强。这些结果表明 FGF14 在某些空间学习功能和突触可塑性中发挥作用 (c) 2006 Elsevier Inc. 保留所有权利。
Spinocerebellar ataxia 27 (SCA27) is a recently described syndrome characterized by impaired cognitive abilities and a slowly progressive ataxia. SCA27 is caused by an autosomal dominant missense mutation in Fibroblast Growth Factor 14 (FGF14). Mice lacking FGF14 (Fgf14(-/-) mice) have impaired sensorimotor functions, ataxia and paroxysmal dyskinesia, a phenotype that led to the discovery of the human mutation. Here we extend the similarities between Fgf14(-/-) mice and FGF14(F145S) humans by showing that Fgf14(-/-) mice exhibit reliable acquisition (place learning) deficits in the Morris water maze. This cognitive deficit appears to be independent of sensorimotor disturbances and relatively selective since Fgf14(-/-) mice performed similarly to wild type littermates during cued water maze trials and on conditioned fear and passive avoidance tests. Impaired theta burst initiated long-term synaptic potentiation was also found in hippocampal slices from Fgf14(-/-) mice. These results suggest a role for FGF14 in certain spatial learning functions and synaptic plasticity (c) 2006 Elsevier Inc. All rights reserved.