Scientific Understanding of Consciousness
Consciousness as an Emergent Property of Thalamocortical Activity

Overlapping Memory Trace Linking, but Not Recalling, Individual Memories


Science  27 Jan 2017: Vol. 355, Issue 6323, pp. 398-403

Overlapping memory trace indispensable for linking, but not recalling, individual memories

Jun Yokose,

Department of Biochemistry, Faculty of Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.

Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.

Division of Animal Experimental Laboratory, Life Science Research Centre, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.

Department of Neuroscience, Jikei University School of Medicine, Tokyo 105-8461, Japan.

Department of Pathology, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.


Memories are not stored in isolation from other memories but are integrated into associative networks. However, the mechanisms underlying memory association remain elusive. Using two amygdala-dependent behavioral paradigms—conditioned taste aversion (CTA) and auditory-cued fear conditioning (AFC)—in mice, we found that presenting the conditioned stimulus used for the CTA task triggered the conditioned response of the AFC task after natural coreactivation of the memories. This was accompanied through an increase in the overlapping neuronal ensemble in the basolateral amygdala. Silencing of the overlapping ensemble suppressed CTA retrieval-induced freezing. However, retrieval of the original CTA or AFC memory was not affected. A small population of coshared neurons thus mediates the link between memories. They are not necessary for recalling individual memories.

Memories are often stored in interconnected networks of the brain to associate with one another. The simultaneous retrieval of two independent memories sometimes links the original memories, generating a qualitatively new memory. Memory is encoded in a specific cell ensemble that is activated during learning, and individual memories are generally represented by different cell ensembles. Acquisition of a new memory can be modified by the simultaneous and artificial reactivation of a specific neuronal ensemble corresponding to that prestored memory, generating synthetic or false memories. When an association is formed between conditioned and unconditioned stimuli (CS and US, respectively) in Pavlovian conditioning, cell ensembles corresponding to each stimulus overlap, and this is thought to link these stimuli. We investigated the nature of these overlapping neuronal ensembles in the association of memories governed by repeated and simultaneous retrieval.

Mice were trained independently on two behavioral tasks: conditioned taste aversion (CTA) on days 5 and 6 and auditory-cued fear conditioning (AFC) on day 10. After each memory was formed, animals received synchronous and repetitive copresentations of the CS for CTA (saccharin solution as CS1) and that for AFC (tone as CS2) during repeated coretrieval sessions (RCSs) in which the tone was presented as soon as mice licked the nozzle that provides the saccharin solution. The CTA and AFC memories in these mice were comparable with those in control animals throughout the entire session, which did not receive the CS2 (tone) during the RCS.

We analyzed c-Fos expression as a marker of neuronal activity in brain areas shown to be important for the performance of CTA and AFC, including the basolateral amygdala, medial prefrontal cortex, and insular cortex. The number of c-Fos–positive cells in the basolateral amygdala was significantly higher in the coretrieval group than in the control group.

Cellular compartment analysis of temporal activity by use of fluorescence in situ hybridization with Arc and Homer 1a (Arc/H1a catFISH) revealed a dynamic interaction between CTA and AFC at the neuronal ensemble level in all the brain areas analyzed.

Our study reveals that repetitive coretrieval    reorganizes two aversive memory traces    to generate an intersectional neuronal ensemble,    neurons shared by both prestored CTA and AFC memories. The overlapping ensemble is responsible for memory association but is dispensable for the retrieval of original memories. An increase in overlapping ensembles has been observed when memories are associated in a variety of learning paradigms. Moreover, memories for events occurring close together in time generate an interaction that accompanies an overlap in the cell ensembles of each memory. Memory trace is not always allocated at the primary active neurons and could be potentially reallocated to the different subsets of neuronal ensembles. The increase in the overlap between CTA and AFC ensembles suggests that the overlapping ensemble is newly formed by the RCS. Thus, after the RCS, CTA and AFC memory traces are reallocated and reorganized to form a memory linkage. Generating an overlapping neuronal ensemble is a general mechanism underlying a linkage between memories during both acquisition and retrieval. Our finding of an overlapping ensemble that is responsible for memory association but dispensable for retrieval of original memories may provide a way to dissociate daily memories that relate in some way to the circumstances of a trauma from a traumatic event. This could help prevent flashback in individuals with posttraumatic stress disorder.

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