Unconsciously implanted memory in the presence of cholecystokinin retrieved in a behaviorally relevant context

Abstract

Previous studies demonstrated that the perirhinal and entorhinal cortices in the hippocampus serve as the gateway for relaying information from the hippocampus system to the neocortex. Specifically, it was found that Cholecyctokinin (CCK), a neuropeptide which is abundant in the perirhinal and entorhinal cortices, enabled neuroplasticity in the auditory cortex through cortical projections of the hippocampus. Another study showed that the cross-modal association can be established in the auditory cortex, which enabled auditory neurons to respond to the visual stimulus. This visuo-auditory association drove animal’s behavior in an auditory rewarding task, addressing the influence of the neuronal changes on the behavioral outcomes. More importantly, the application of CCK antagonist in the auditory cortex prevented the establishment of visuo-auditory association, suggesting that the neuroplasticity in the cortex is CCK dependent. Together with these findings, we postulate that the CCK-induced neuroplasticity in the auditory cortex leads to relative behavioral changes. A series of experiments were conducted to address this hypothesis. Rats implanted bilaterally with electrodes and injection cannula in the auditory cortex were trained to approach the left or right hole of a behavioral apparatus to retrieve a physical reward depending on whether the right or left auditory cortex was electrically stimulated. Next, under anesthesia, a previously irrelevant light stimulus was repeatedly paired with electrical stimulation at one side of the auditory cortex in the presence of CCK, after which auditory neurons started to respond to the light stimulus in both anesthetized and awake states. In the following behavioral testing, when the light stimulus was presented instead of electrical stimulation, rats approached the hole that was "engineered" to be associated with reward availability. Besides, several control experiments were performed to validate the results and eliminate the non-specific effects of drug application and other manipulations. Finally we found that the visuo-auditory association induced by CCK was reflected in behavioral context, supporting the hypothesis arisen from the previous studies. These findings provide a scientific foundation for "memory implantation".