RIM1alpha and interacting proteins involved in presynaptic plasticity mediate prepulse inhibition and additional behaviors linked to schizophrenia.
RIM1alpha and interacting proteins involved in presynaptic plasticity mediate prepulse inhibition and additional behaviors linked to schizophrenia.
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DOI：
10.1523/jneurosci.0328-10.2010
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发表时间：
2010-04-14
期刊：
影响因子：
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通讯作者：
Powell CM
中科院分区：
文献类型：
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作者：
Blundell J;Kaeser PS;Südhof TC;Powell CM
几种与中枢神经系统神经递质释放有关的突触前蛋白在人类临床遗传学研究、尸检研究和精神分裂症假定动物模型的研究中被认为与精神分裂症有关。突触前蛋白RIM1α介导突触前可塑性和认知功能。我们现在证明，缺乏RIM1α的小鼠在多个与精神分裂症相关的行为任务中表现出异常，包括脉冲前抑制、对精神分裂药物的反应和社会互动。这些与精神分裂症相关的行为发现对RIM1α缺陷小鼠具有相对选择性，因为携带RIM1α结合伙伴Rab3A或突触素1突变的小鼠只显示脉冲前抑制减少。除了RIM1α的S参与了多种行为异常外，这些数据还表明，突触前形式的短期可塑性的变化与脉冲前抑制的变化有关，脉冲前抑制是一种衡量感觉运动门控的指标。
Several presynaptic proteins involved in neurotransmitter release in the central nervous system have been implicated in schizophrenia in human clinical genetic studies, in post-mortem studies, and in studies of putative animal models of schizophrenia. The presynaptic protein RIM1α mediates presynaptic plasticity and cognitive function. We now demonstrate that mice deficient in RIM1α exhibit abnormalities in multiple schizophrenia-relevant behavioral tasks including prepulse inhibition, response to psychotomimetic drugs, and social interaction. These schizophrenia-relevant behavioral findings are relatively selective to RIM1α deficient mice, as mice bearing mutations in the RIM1α binding partners Rab3A or synaptotagmin 1 only show decreased prepulse inhibition. In addition to RIM1α’s involvement in multiple behavioural abnormalities, these data suggest that alterations in presynaptic forms of short-term plasticity are linked to alterations in prepulse inhibition, a measure of sensorimotor gating.