Hippocampal and cortical primary cilia are required for aversive memory in mice.
Hippocampal and cortical primary cilia are required for aversive memory in mice.
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DOI：
10.1371/journal.pone.0106576
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Yoder BK
中科院分区：
文献类型：
--
作者：
Berbari NF;Malarkey EB;Yazdi SM;McNair AD;Kippe JM;Croyle MJ;Kraft TW;Yoder BK
几十年来，人们已经知道整个大脑的神经元拥有独立的、不动的、基于微管的附属物，称为初级纤毛。直到最近才有研究试图解决这些纤毛的功能，但我们目前的了解仍然很薄弱。为了确定神经元纤毛是否在行为中发挥作用，我们通过有条件删除鞭毛内转运 88 (Ift88) 基因，特意破坏了小鼠皮质和海马的纤毛发生。使用莫里斯水迷宫和恐惧调节范式分析对学习和记忆的影响。与野生型对照相比，纤毛突变体在厌恶性学习和记忆以及新物体识别方面表现出缺陷。此外，突变体的海马神经元表现出改变的配对脉冲反应，表明 IFT88 的缺失可以改变突触特性。各种其他行为测试显示条件纤毛突变体和对照之间没有显着差异。这种类型的条件等位基因方法可用于区分纤毛病的哪些行为特征是由于神经发育缺陷引起的，哪些是由细胞生理学改变引起的。最终，这可能会导致人们更好地了解与人类纤毛疾病（如巴代-比德尔综合征）以及可能更常见的疾病（包括抑郁症和精神分裂症）相关的认知缺陷的基础。
It has been known for decades that neurons throughout the brain possess solitary, immotile, microtubule based appendages called primary cilia. Only recently have studies tried to address the functions of these cilia and our current understanding remains poor. To determine if neuronal cilia have a role in behavior we specifically disrupted ciliogenesis in the cortex and hippocampus of mice through conditional deletion of the Intraflagellar Transport 88 (Ift88) gene. The effects on learning and memory were analyzed using both Morris Water Maze and fear conditioning paradigms. In comparison to wild type controls, cilia mutants displayed deficits in aversive learning and memory and novel object recognition. Furthermore, hippocampal neurons from mutants displayed an altered paired-pulse response, suggesting that loss of IFT88 can alter synaptic properties. A variety of other behavioral tests showed no significant differences between conditional cilia mutants and controls. This type of conditional allele approach could be used to distinguish which behavioral features of ciliopathies arise due to defects in neural development and which result from altered cell physiology. Ultimately, this could lead to an improved understanding of the basis for the cognitive deficits associated with human cilia disorders such as Bardet-Biedl syndrome, and possibly more common ailments including depression and schizophrenia.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
5.3
作者：
Eichers, Erica R.;Abd-El-Barr, Muhammad M.;Lupski, James R.
通讯作者：
Lupski, James R.
影响因子：
4.5
作者：
Li, Chunmei;Inglis, Peter N.;Leitch, Carmen C.;Efimenko, Evgeni;Zaghloul, Norann A.;Mok, Calvin A.;Davis, Erica E.;Bialas, Nathan J.;Healey, Michael P.;Heon, Elise;Zhen, Mei;Swoboda, Peter;Katsanis, Nicholas;Leroux, Michel R.
通讯作者：
Leroux, Michel R.
影响因子：
3.3
作者：
Händel, M;Schulz, S;Höllt, V
通讯作者：
Höllt, V
影响因子：
2.7
作者：
Berbari NF;Kin NW;Sharma N;Michaud EJ;Kesterson RA;Yoder BK
通讯作者：
Yoder BK