PDF(Pubmed)
Abstract：
Neurexins (Nrxns) are critical for synapse organization and their mutations have been documented in autism spectrum disorder, schizophrenia, and epilepsy. We recently reported that conditional deletion of Nrxn2, under the control of Emx1Cre promoter, predominately expressed in the neocortex and hippocampus (Emx1-Nrxn2 cKO mice) induced stereotyped patterns of behavior in mice, suggesting behavioral inflexibility. In this study, we investigated the effects of Nrxn2 deletion through two different conditional approaches targeting presynaptic cortical neurons projecting to dorsomedial striatum on the flexibility between goal-directed and habitual actions in response to devaluation of action-outcome (A-O) contingencies in an instrumental learning paradigm or upon reversal of A-O contingencies in a water T-maze paradigm. Nrxn2 deletion through both the conditional approaches induced an inability of mice to discriminate between goal-directed and habitual action strategies in their response to devaluation of A-O contingency. Emx1-Nrxn2 cKO mice exhibited reversal learning deficits, indicating their inability to adopt new action strategies. Overall, our studies showed that Nrxn2 deletion through two distinct conditional deletion approaches impaired flexibility in response to alterations in A-O contingencies. These investigations can lay the foundation for identification of novel genetic factors underlying behavioral inflexibility.
摘要：
Neurexins（Nrxns）对于突触组织至关重要，它们的突变已在自闭症谱系障碍中得到记录，精神分裂症,和癫痫。我们最近报道了在Emx1Cre启动子控制下Nrxn2的条件性缺失，主要在新皮层和海马中表达（Emx1-Nrxn2cKO小鼠）诱导小鼠的刻板行为模式，表明行为不灵活。在这项研究中,我们通过两种不同的条件方法研究了Nrxn2缺失对目标导向和习惯性动作之间的灵活性的影响，这些方法针对投射到背纹状体的突触前皮层神经元，在工具性学习范式中或在水T迷宫范式中A-O突发事件逆转时。通过两种条件方法删除Nrxn2导致小鼠无法区分目标导向和习惯性行动策略，以应对A-O偶然性的贬值。Emx1-Nrxn2cKO小鼠表现出逆转学习缺陷，表明他们无法采取新的行动战略。总的来说,我们的研究表明,Nrxn2通过两种不同的条件性缺失方法的缺失降低了对A-O偶然性改变的反应灵活性.这些研究可以为识别行为不灵活性的新遗传因素奠定基础。
