【作者】 张晨风； 陈祥茂； 龙程； 杨莉；

【Author】 Chenfeng Zhang;Xiangmao Chen;Cheng Long;Li Yang;School of Psychology,South China Normal University;School of Life Sciences, South China Normal University;

【机构】 华南师范大学心理学院； 华南师范大学生命科学学院；

【摘要】 注意力通常被定义为是一种在复杂环境中选择有效信息,忽略无关刺激的行为及认知过程。已有的研究发现阿尔茨海默症患者在发病早期已表现出注意力受损,但具体的神经机制仍然不清楚。APP, PS1基因是两种与阿尔茨海默症相关的致病基因,鉴于人类被试的局限性,我们采用了被广泛认可的阿尔茨海默症动物模型、APP/PS1小鼠作为实验对象,从行为、细胞及分子层面展开研究。行为层面我们基于行为主义理论中的操作性条件反射概念,利用斯金纳箱作为实验场景,箱中配备鼻触,食物槽,扬声器等刺激条件,并参照连续性操作范式进行编程,设计出一套完整的以食物作为强化的任务范式。小鼠在任务执行中的各个反应可被拿来作为评价注意力功能的指标。实验结果发现,与正常的野生型小鼠WT相比,APP/PS1小鼠在第三阶段学习所花时间更长,对正确刺激的辨别力和持续性注意力均显著低于WT小鼠。内侧前额叶皮层是负责注意力的关键脑区,脑片全细胞膜片钳结果显示APP/PS1小鼠内侧前额叶皮层微小抑制性突触后电位和自发抑制性突触后电位均显著高于WT小鼠,说明内侧前额叶皮层兴奋性降低。鉴于已有的研究发现内侧前额叶皮层亚区PL部位的兴奋是冲动控制的重要脑区,上述结果提示造成APP/PS1小鼠上述行为差异的主要原因可能不是学习能力的低下,而是APP/PS1小鼠内侧前额叶皮层的抑制控制能力更弱,无法阻止干扰信息。更多还原

【Abstract】 Attention may be defined as the behavioral and cognitive process that allows us to select the information present in our environment along with the ability to ignore irrelevant stimuli. Initial studies suggested that attention is impaired in the early stage of Alzheimer’s disease(AD), while the mechanisms underlying such alteration are poorly understood. The APP and PS1 mutations are thought to be responsible for the pathogenesis of AD. Given the limitation of human subjects, in this experiment we choose APP/PS1 double transgenic mice, a widely used AD model as our subjects. Based on the concept of operant conditioning in behaviorism, behavioural tests were conducted in the Skinner box equipped with nosepork touching, reward pool and speaker as stimuli. We designed a protocol which consists of three different learning sessions. Various responses were used as indicators to evaluate attention function. We show, in the present study, that APP/PS1 mice spent more time and demonstrated significantly lower discrimination index and sustained attention scores compared to WT controls in stage 3. Whole-cell patch recording showed increased sIPSC and mIPSC frequency in APP/PS1 brain slices in PFC, which is part of the neural regions strongly involved in attention procession. Consider that the excitation of PFC plays a critical role in inhibitory behavior and thus in the control of impulsivity, our data suggest that the attention deficit seen in APP/PS1 mice may be due, at least in part, to alterations in inhibition control ability, rather than learning ability.更多还原