New Translational Procedure to Study Retroactive Interference and Memory Updating Mechanisms in Mice
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Memories are not fixed entities but change in a course of new experiences. Evidence that memories are subject to modification is supported by a large body of work in cognitive psychology demonstrating that presentation of new competing information at the time of retrieval can lead to distortion or impairment of old memories. Although the constructive nature of memory is now well established, the underlying cellular mechanisms remain poorly understood. Here, we introduce a new translation task for rodents that provides a way to study memory-updating mechanisms and retroactive interference phenomenon, the most common cause of forgetting. The task is conducted in an operant chamber and involves spontaneous discrimination of novel from familiar nose-poke modules that are distinguishable by their visual feature and spatial location. In the acquisition session, mice are exposed for the first time to the testing chamber with one blinking nose-poke module. In the choice session, a novel non-blinking nose-poke module is inserted into an empty spatial location and the preference for novel over the familiar nose-poke modules (number of nose poking) is used as an index of recognition memory. We first demonstrate that recognition performance varies as a function of the length of the acquisition period and the retention delay and is sensitive to conventional amnestic treatments (muscarinic receptor and NMDA receptor antagonists, scopolamine and MK-801, respectively). We next manipulated the features of spatial context during a brief reactivation episode (insufficient for acquiring a new context recognition memory) to study memory updating mechanisms. We show that presentation of new competing information during retrieval impairs subsequent recall of old memory as reported by studies in normal human subjects and provide evidence that mnemonic integration can occur either by a consolidation or a reconsolidation mechanism to update pre-existing memory representation. We further demonstrate that both forms of memory updating do not overwrite previously stored information and that memory impairments are due to retrieval failure caused by retroactive interference.
