Iacoangeli Anna, Dosunmu Aderemi, Eom Taesun, Stefanov Dimitre G, Tiedge Henri
The Robert F. Furchgott Center for Neural and Behavioral Science, State University of New York Downstate Medical Center, Brooklyn, New York 11203, USA.
Department of Physiology and Pharmacology, State University of New York Downstate Medical Center, Brooklyn, New York 11203, USA.
Learn Mem. 2017 Jun 15;24(7):267-277. doi: 10.1101/lm.045427.117. Print 2017 Jul.
Dendritic regulatory BC1 RNA is a non-protein-coding (npc) RNA that operates in the translational control of gene expression. The absence of BC1 RNA in BC1 knockout (KO) animals causes translational dysregulation that entails neuronal phenotypic alterations including prolonged epileptiform discharges, audiogenic seizure activity in vivo, and excessive cortical oscillations in the γ frequency band. Here we asked whether BC1 RNA control is also required for higher brain functions such as learning, memory, or cognition. To address this question, we used odor/object attentional set shifting tasks in which prefrontal cortical performance was assessed in a series of discrimination and conflict learning sessions. Results obtained in these behavioral trials indicate that BC1 KO animals were significantly impaired in their cognitive flexibility. When faced with conflicting information sources, BC1 KO animals committed regressive errors as they were compromised in their ability to disengage from recently acquired memories even though recall of such memories was in conflict with new situational context. The observed cognitive deficits are reminiscent of those previously described in subtypes of human autism spectrum disorders.
树突状调节性BC1 RNA是一种非蛋白质编码（npc）RNA，在基因表达的翻译控制中发挥作用。BC1基因敲除（KO）动物中BC1 RNA的缺失会导致翻译失调，进而引发神经元表型改变，包括癫痫样放电延长、体内听源性癫痫活动以及γ频段的过度皮层振荡。在这里，我们探讨了BC1 RNA调控对于诸如学习、记忆或认知等高级脑功能是否也是必需的。为了解决这个问题，我们使用了气味/物体注意力转换任务，在一系列辨别和冲突学习环节中评估前额叶皮层的表现。在这些行为试验中获得的结果表明，BC1基因敲除动物的认知灵活性显著受损。当面对相互冲突的信息源时，BC1基因敲除动物会出现退行性错误，因为它们在脱离最近获得的记忆方面存在缺陷，即使回忆这些记忆与新的情境相冲突。观察到的认知缺陷让人联想到先前在人类自闭症谱系障碍亚型中描述的那些缺陷。
