Phenotype of Mice With Inducible Ablation of GluA1 AMPA Receptors During Late Adolescence: Relevance for Mental Disorders
Phenotype of Mice With Inducible Ablation of GluA1 AMPA Receptors During Late Adolescence: Relevance for Mental Disorders
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DOI：
10.1002/hipo.22236
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发表时间：
2014-04-01
期刊：
影响因子：
3.5
通讯作者：
Gass, Peter
中科院分区：
文献类型：
--
作者：
Inta, Dragos;Vogt, Miriam A.;Gass, Peter
青春期的特点是重要的分子和解剖学的变化与成熟的大脑回路和认知功能。这段时间对于出现几种伴有认知障碍的神经精神障碍，如情感障碍和精神分裂症至关重要。然而，在这个特定的发育阶段，神经元水平上这些变化的分子机制仍然知之甚少。含有GluA1的AMPA受体主要位于海马神经元上，是突触可塑性的主要分子决定因素。在这里，我们调查的后果，诱导删除GluA1 AMPA受体在adenamatergic神经元在青春期后期。我们产生的突变小鼠与他莫昔芬诱导的GluA1缺失的CamKII启动子的控制下，时间和空间限制的基因操作。GluA1消融在青春期后期引起认知障碍，但也显着hypermotion和感觉运动门控缺陷。与GluA1的整体基因缺失不同，青春期后期的诱导型GluA1消融导致正常的社交能力。GluA1的缺失导致GluA2亚基的重新分布，表明AMPA受体运输缺陷。突变动物海马NMDA受体表达增加，纹状体多巴胺浓度无变化。我们的数据提供了新的见解缺乏AMPA受体的作用，特别是在青春期后期诱导几个认知和行为的改变，可能与神经精神疾病。(c)2013 Wiley Periodicals，Inc.
Adolescence is characterized by important molecular and anatomical changes with relevance for the maturation of brain circuitry and cognitive function. This time period is of critical importance in the emergence of several neuropsychiatric disorders accompanied by cognitive impairment, such as affective disorders and schizophrenia. The molecular mechanisms underlying these changes at neuronal level during this specific developmental stage remains however poorly understood. GluA1-containing AMPA receptors, which are located predominantly on hippocampal neurons, are the primary molecular determinants of synaptic plasticity. We investigated here the consequences of the inducible deletion of GluA1 AMPA receptors in glutamatergic neurons during late adolescence. We generated mutant mice with a tamoxifen-inducible deletion of GluA1 under the control of the CamKII promoter for temporally and spatially restricted gene manipulation. GluA1 ablation during late adolescence induced cognitive impairments, but also marked hyperlocomotion and sensorimotor gating deficits. Unlike the global genetic deletion of GluA1, inducible GluA1 ablation during late adolescence resulted in normal sociability. Deletion of GluA1 induced redistribution of GluA2 subunits, suggesting AMPA receptor trafficking deficits. Mutant animals showed increased hippocampal NMDA receptor expression and no change in striatal dopamine concentration. Our data provide new insight into the role of deficient AMPA receptors specifically during late adolescence in inducing several cognitive and behavioral alterations with possible relevance for neuropsychiatric disorders. (c) 2013 Wiley Periodicals, Inc.