Dissociating the effects of distraction and proactive interference on object memory through tests of novelty preference

Abstract

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.

Maternal immune activation affects female offspring whisker movements during object exploration in a rat model of neurodevelopmental disorders

“…This is the first time we have observed significant treatment effects on whisker movements with different objects. An identical sequential object exploration task was used by Landreth et al (2021) in a sub-chronic PCP rat model of schizophrenia and did not reveal any differences between the smooth and textured objects. It is worth noting that the objects were very similar and only differed in colour and texture ( Supplementary material C, Fig.…”

“…For high-speed filming of whisker movements, a sequential object exploration task was adopted ( Supplementary material C , Fig. S1 ), exact details of which can be found in Landreth et al (2021) . Observers were blind to the rat treatment group throughout the video collection and analysis process.…”