A Study On The Effect Of Activation-reduction On Fear Memory In Different Time Periods

Fear conditioning paradigm is an important behavioral model to study the processes of fear acquisition,consolidation,storage,extraction and re-consolidation,which is based on Pavlovian fear conditioning.It has been proposed as an important factor involved in the etiology of PTSD.Contextual fear conditioning and cued fear conditioning are two typical paradigms.Behavioral erasure of fearful memories has long been pursued as an effective way to treat anxiety disorders.Monfils et al.(2009)suggested a behavioral way to erase fear memories,by providing a brief reminder before extinction(retrieval-extinction)that is done 24h or longer after contextual fear conditioning.In this study,we selected ICR mice as the research object,by using a contextual fear conditioning paradigm,we investigated the effects of the retrieval-extinction on fear memories which acquired with different stress intensity,and whether the effects of the retrieval-extinction on fear memories are modulated by memory age.Behavioral test,FD rapid Golgi-staining and immunohistochemistry methods were used to examine these two purposes.This study found that:(1)Contextual fear memories are a fast-consolidating process under high stress intensity,and there is no significant difference in the expression of fear memories after 1-day,5-day,14-day,35-day and 39-day's training for the mice's fear conditioning.Contextual fear memories are a gradual/slow-consolidating process under low stress intensity,the expression of fear memories after 1-day,14-day's training is significantly different with 39-day's training,and the expression test of fear conditioning memories tend to increase in each group.(2)Retrieval-extinction can block re-consolidation of remote fear memories under high stress intensity,and this model can significantly decrease the fear memory of remote group in the extinction test and the spontaneous recovery test.Retrieval-extinction can block re-consolidation of recent fear memories under low stress intensity,and this model can also significantly decrease the fear memory of recent group in the extinction test and the spontaneous recovery test.(3)Remote fear memories are easier to re-activate under high stress intensity.In the hippocampus CA1 and amygdala BLA regions,neuron dendritic spine's density in remote group is significantly lower than recent group.In contrast,recent fear memories are easier to re-activate under low stress intensity.In the hippocampus CA1 and amygdala BLA regions,neuron dendritic spine's density in recent group is significantly lower than remote group.(4)Memory retrieval under high stress intensity facilitates the elimination of remote fear memories.After memory retrieval,in hippocampus CA1 region,remote group 's c-Fos+ cells are significantly lower than recent group's.Memory retrieval under low stress intensity facilitates the elimination of recent fear memories.After memory retrieval,in hippocampus CA1 and amygdala BLA regions,recent group's Zif268+ and c-Fos+ cells are significantly lower than remote group's.This study shows that retrieval-extinction model's effects toward recent and remote fear memories are modulated by the stress intensity.That is to say,we should postpone the time for behavioral intervention when we experience high-intensity stress events,while we should conduct behavioral intervention immediately when we experience low-intensity stress events.Our results also provide a direction and a new theory foundation for further research.