Behavioral and immunohistochemical characterization of rapid reconditioning following extinction of contextual fear.

A fundamental property of extinction is that the behavior that is suppressed during extinction can be unmasked through a number of postextinction procedures. Of the commonly studied unmasking procedures (spontaneous recovery, reinstatement, contextual renewal, and rapid reacquisition), rapid reacquisition is the only approach that allows a direct comparison between the impact of a conditioning trial before or after extinction. Thus, it provides an opportunity to evaluate the ways in which extinction changes a subsequent learning experience. In five experiments, we investigate the behavioral and neurobiological mechanisms of postextinction reconditioning. We show that rapid reconditioning of unsignaled contextual fear after extinction in male Long-Evans rats is associative and not affected by the number or duration of extinction sessions that we examined. We then evaluate c-Fos expression and histone acetylation (H4K8) in the hippocampus, amygdala, prefrontal cortex, and bed nucleus of the stria terminalis. We find that in general, initial conditioning has a stronger impact on c-Fos expression and acetylation than does reconditioning after extinction. We discuss implications of these results for theories of extinction and the neurobiology of conditioning and extinction.