Context-bridged associative learning: linking neutral tone engram to fear through shared context

Abstract

In associative fear learning, weak or temporally constrained training may fail to link a conditioned stimulus (CS) with an aversive unconditioned stimulus (US), particularly when the contextual representation is impaired (the immediate shock deficit). Here, we systematically tested behavioral conditions that enable linking of an initially neutral auditory memory trace to an aversive episode. Male C57BL/6 mice were studied in four experiments manipulating (i) preexposure to a CS tone, (ii) the duration of context exploration before immediate footshock, and (iii) whether CS memory was tested in a novel or a familiar-like context. A 5 s tone followed immediately by footshock did not induce reliable fear to either the CS or the training context. CS preexposure three days before conditioning did not facilitate CS aversive memory when animals were tested in a completely novel context. However, robust facilitation emerged when the CS memory was tested in a context similar to the preexposure/conditioning one, indicating strong contextual gating of CS retrieval. Extending context exploration before shock enabled CS fear learning, but reduced (and even reversed) the effect of CS preexposure, consistent with latent inhibition. Together, these results delineate behavioral constraints for linking an initially neutral cue memory to an aversive event and highlight contextual control over the coupling and expression of cue memory traces.