Encoding,Consolidation,Retrieval and Intervention of Conditioned Fear Extinction Memory
Exposure interventions based on the principles of extinction are effective methods for the treatment of anxiety disorders,but some patients still have problems such as spontaneous recovery,renewal,and reinstatement of fear.Therefore,how to promote and maintain fear extinction has been the key and difficulty of this field.Fear extinction refers to the formation of a new extinction memory established by presenting the conditioned stimulus(CS)repeatedly without the unconditioned stimulus(US).Good extinction learning is manifested not only in successful extinction,but also in retention of learned safety responses during subsequent extinction recall.This suggests that we need to explore the neural basis of extinction memory encoding,consolidation,and retrieval stages separately.The purpose of this paper is to discuss the effective intervention methods at each stage on the basis of systematically expounding the neural mechanism of memory extinction,and to provide some guidance for clinical treatment.The Basolateral amygdala(BLA),infralimbic(IL)region of the prefrontal cortex,hippocampus,and the Dopamine(DA)system of the Ventral Tegmental Area(VTA)play distinct roles in the extinction of Pavlovian conditioned fear.(1)Successful extinction coding depends on the formation of"extinction memory neurons"in the BLA and the DA activity caused by anticipation errors.Furthermore,we suggest that the formation of"extinction memory neurons"in the BLA is regulated by DA caused by anticipation errors,but the neural circuit of this regulatory process is currently unclear.(2)The consolidation of extinction memory is mainly dependent on infralimbic-centered neural circuits,including the BLA,hippocampus,and DA system.The BLA mainly transmits the CS+-no US conditioned connection,the hippocampus inputs extinction memory context information,and DA is a key regulator of IL spontaneous activity.(3)The success of retrieval in extinction memory depends on whether the fear circuit or the extinction circuit is activated.There is another case of successful extinction recall:when CS+is presented alone,it evokes fear memory but is immediately inhibited,that is,the retrieval stopping model,indicating that the individual consciously prevents negative thought intrusion.The two retrieval circuits do not conflict,and the prefrontal cortex is the center that provides inhibition.According to the neural mechanism of extinction memory,we explore the intervention methods for different stages.Enhancing anticipatory errors during extinction learning and oral administration of DCS before extinction learning can enhance extinction memory encoding.To enhance extinction memory consolidation,neuromodulation,and L-DOPA after extinction learning are considered to be effective approaches.In addition,it can also be combined with proper exercise,and good sleep.In conclusion,although there are some methods of intervening in memory extinction,it is still necessary to explore diverse methods to maximize the optimization of clinical treatment.The following aspects should be considered in future research.(1)Extinction memory traces weaken over time and are impaired in non-extinction contexts,suggesting that we need to deepen extinction memory traces and promote extinction generalization in the future.(2)Future research needs to continue to expand the neural mechanism of extinction memory at each stage,including enriching the neural mechanism of memory coding,exploring the regulation mechanism of the dopamine system,and the effect of prefrontal activity during sleep on consolidation.(3)Interfering with extinction memory retrieval is a new direction to enhance fear,such as the use of neuromodulation,positive emotion induction,and repetition strategies.
NETL
NSTL
万方数据
