通过新颖性偏好测试分离分心和主动干扰对对象记忆的影响

Katie Landreth, Ugne Simanavicuite, Jennifer Fletcher, Ben Grayson, Robyn A. Grant, Micheal Harte, John Gigg
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引用次数: 1

摘要

将信息编码到内存中对分心很敏感,而检索内存可能会受到来自预先存在的内存的主动干扰。这两种使人衰弱的影响在神经精神疾病中很常见,但迄今为止,对它们进行临床前建模是缓慢的,因为它需要长时间的操作训练。一个步骤的改变是基于自发行为验证功能等效但快速、简单、高通量的任务。在这里,我们表明,在亚慢性苯环利定大鼠精神分裂症相关认知障碍模型中,自发对象偏好测试符合这些要求。亚慢性苯环利定大鼠在标准的新物体识别任务中对分心表现出明显的记忆敏感性。然而,由于这一点,标准的新型物体识别任务无法评估主动干扰。因此,我们将标准新对象识别任务中的亚慢性苯环利定性能与使用连续新对象识别的任务进行了比较,后者提供了最小的干扰,可以直接评估与疾病相关的记忆缺陷。我们首先确定,在物体探索过程中,亚慢性苯环利定处理不会影响胡须的运动。亚慢性苯环利定大鼠表现出预期的分心标准新对象识别任务效果,但在第一次连续的新对象识别实验中表现良好,使用两种新对象识别工作变体有效地解离了分心。在剩余的连续新物体识别任务试验中,亚慢性苯环利定大鼠的累积判别指数始终高于偶然性,但重要的是,与对照组相比,它们对物体新颖性的检测越来越受损。我们将这种影响归因于主动干扰的积累。这是首次证明,在亚慢性苯环利定大鼠中,使用相同快速、简单、自发对象记忆范式的两种变体,可以分离出对分心和主动干扰这两种精神分裂症关键认知障碍的敏感性增加。
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Dissociating the effects of distraction and proactive interference on object memory through tests of novelty preference
Encoding information into memory is sensitive to distraction while retrieving that memory may be compromised by proactive interference from pre-existing memories. These two debilitating effects are common in neuropsychiatric conditions, but modelling them preclinically to date is slow as it requires prolonged operant training. A step change would be the validation of functionally equivalent but fast, simple, high-throughput tasks based on spontaneous behaviour. Here, we show that spontaneous object preference testing meets these requirements in the subchronic phencyclidine rat model for cognitive impairments associated with schizophrenia. Subchronic phencyclidine rats show clear memory sensitivity to distraction in the standard novel object recognition task. However, due to this, standard novel object recognition task cannot assess proactive interference. Therefore, we compared subchronic phencyclidine performance in standard novel object recognition task to that using the continuous novel object recognition task, which offers minimal distraction, allowing disease-relevant memory deficits to be assessed directly. We first determined that subchronic phencyclidine treatment did not affect whisker movements during object exploration. Subchronic phencyclidine rats exhibited the expected distraction standard novel object recognition task effect but had intact performance on the first continuous novel object recognition task trial, effectively dissociating distraction using two novel object recognition task variants. In remaining continuous novel object recognition task trials, the cumulative discrimination index for subchronic phencyclidine rats was above chance throughout, but, importantly, their detection of object novelty was increasingly impaired relative to controls. We attribute this effect to the accumulation of proactive interference. This is the first demonstration that increased sensitivity to distraction and proactive interference, both key cognitive impairments in schizophrenia, can be dissociated in the subchronic phencyclidine rat using two variants of the same fast, simple, spontaneous object memory paradigm.
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