In vivo imaging of dendritic spines in learning and unlearning

Abstract

The ability to associate danger with environmental stimuli is essential for animal survival, while adapting to new rules is equally important. However, how the neuronal network enables such flexibility in fear responses is still unknown. Our previous findings show that fear learning and unlearning induce reversible dendritic spine plasticity in the frontal association cortex. Here we will use auditory-cued fear conditioning and extinction as learning paradigms to investigate how learning and unlearning of fear toward auditory cues affect the auditory cortex dendritic spine plasticity. By using in vivo transcranial imaging technique, we found that fear conditioning induced dendritic spine formation in the mouse auditory cortex. In contrast, fear extinction induced dendritic spine elimination and the newly-formed spines induced by fear conditioning were preferentially eliminated. These data suggested that the fear learning memory traces were preferentially erased. In addition, fear extinction training extinguished cue-specific freezing response and the newly formed spines that were eliminated were also cue-specific. These results showed that fear conditioning and extinction induced cue-specific dendritic spine formation and elimination in the auditory cortex. Furthermore, reconditioning of the same auditory cue that has been extinguished induced re-formation of dendritic spines located in close proximity to the previous spine formation site. Taken together, our findings suggest that fear learning and unlearning lead to opposite and reversible dendritic plasticity in mouse neocortex in a cue- and location-specific manner.