Landreth K, Simanaviciute U, Fletcher J, Grayson B, Grant R A, Harte M H, Gigg J
Division of Neuroscience and Experimental Psychology, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.
Department of Natural Sciences, Manchester Metropolitan University, Manchester, UK.
Brain Neurosci Adv. 2021 Apr 27;5:23982128211003199. doi: 10.1177/23982128211003199. eCollection 2021 Jan-Dec.
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.
将信息编码到记忆中对干扰很敏感,而提取该记忆可能会受到先前存在的记忆的前摄干扰的影响。这两种削弱性影响在神经精神疾病中很常见,但迄今为止在临床前对其进行建模进展缓慢,因为这需要长时间的操作性训练。一个重大转变将是基于自发行为对功能等效但快速、简单、高通量的任务进行验证。在这里,我们表明,在与精神分裂症相关的认知障碍的亚慢性苯环利定大鼠模型中,自发物体偏好测试满足这些要求。亚慢性苯环利定大鼠在标准新颖物体识别任务中对干扰表现出明显的记忆敏感性。然而,正因为如此,标准新颖物体识别任务无法评估前摄干扰。因此,我们将亚慢性苯环利定在标准新颖物体识别任务中的表现与使用连续新颖物体识别任务的表现进行了比较,该任务提供的干扰最小,从而可以直接评估与疾病相关的记忆缺陷。我们首先确定,亚慢性苯环利定治疗不会影响物体探索过程中的触须运动。亚慢性苯环利定大鼠表现出预期的干扰标准新颖物体识别任务效应,但在第一次连续新颖物体识别任务试验中表现完好,有效地使用两种新颖物体识别任务变体分离了干扰。在其余的连续新颖物体识别任务试验中,亚慢性苯环利定大鼠的累积辨别指数始终高于随机水平,但重要的是,相对于对照组,它们对物体新颖性的检测越来越受损。我们将这种效应归因于前摄干扰的积累。这是首次证明,对干扰和前摄干扰的敏感性增加,这两种精神分裂症的关键认知障碍,可以在亚慢性苯环利定大鼠中使用相同的快速、简单、自发物体记忆范式的两种变体进行分离。