The Neural Circuits From Hippcampus To The Bed Nucleus Of Stria Terminalis Participate In The Formation Of Contextual Fear Memory

BackgroundIn order to survive,the body needs to change their behavior according to the environment flexibly.It's a good performance for protecting themselves when the human or animal encounters danger,then they behave the subsequent defensive behavior and have the fear emotion.While the fear memory formed by this fear is very important for maintaining the health of the body.Especially for human beings,once this fear memory is formed,it is likely to suffer some mental disorders.Post-traumatic stress disorder(PTSD)is a common mental disorder in humans after suffering some traumatic events.PTSD is a type of mental disorder which has a long course and relapses easily,accordingly it seriously affects the quality of patients' life.Many patients will suffer from self-harm,suicide,and drug abuse,which will cause a serious burden on society.The essence of PTSD is that the formation of fear memory,and the fear memory is difficult to erase,so it's necessary to study the neural circuits of fear memory formation.Contextual fear conditioning(CFC)is a commonly used model for studying fear memory.And Memory includes several different processes,acquisition,consolidation,retrieval,extinction,etc.,in which acquisition,consolidation and retrieval are also called memory formation.Therefore,to understand the neural circuit of the contextual fear memory is very important for understanding the formation of PTSD.In the past few years,there are a lot of studies on the neural circuits of contextual fear memory formation.A large number of studies focused on the main three brain regions and their neural circuits,hippocampus(Hippocampus,HPC),the basolateral amygdala(BLA)and the Ventromedial prefrontal cortex(vmPFC),and lots of showed them participated in the formation of contextual fear memory.But whether there are other brain regions and neural circuits involved in the formation of contextual fear memory is not very clear now.For example,how about the neural circuit between the hippocampus and the bed nucleus of the stria terminalis(BNST),which is closely related to stress?If there is the neural circuit between the the hippocampus and bed nucleus of the stria terminalis(BNST),will it play a role in the different processes of contextual fear memory formation?To address this question,we do the neural circuit tracking,and find there are two different neural circuit from HPC to BNST,the dorsal hippocampus(DH)to BNST and the ventral hippocampus(VH)to BNST.Combining with optogenetics and chemical genetics,we inhibit these two neural pathways in different fear memory processes,and we find that DH-BNST pathway participates in the retrieval of contextual fear memory,while VH-BNST participates in the acquisition,consolidation and retrieval of contextual fear memory.This study enriches the study about neural basis of the contextual fear memory and provides some new ideas and references for the formation of PTSD.ObjectiveDiscover the role of neural circuits from HPC to BNST in contextual fear memory formation.Results:1.There are two different neural circuits from HPC to BNST.We used CTB for neuron retrograde tracing.We injected the CTB to BNST,then we found the positive neurons in both DH and VH.These results suggest that there are two different neural circuits from HPC to BNST,DH-BNST and VH-BNST.2.Inhibition of DH-BNST pathway does not affect the acquisition and consolidation of contextual fear memory and but it affects the retrieval of contextual fear memory.We used optogenetics to inhibit DH-BNST neural circuits during contextual fear memory training and retrieval,then we found that inhibition of DH-BNST did not affect the acquisition of contextual fear memory,while it affects the retrieval of contextual fear memory.What's more the mobility of mice is not affected by inhibiting the DH-BNST pathway with optogenetics.We used the DREADD system to selectively silence the DH-BNST pathway after CFC training,then we can see the influence on consolidation of contextual fear memory.We found that inhibition of DH-BNST does not affect the consolidation of contextual fear memory.Also,the mobility of mice is not affected by inhibiting the DH-BNST pathway with chemical genetics.3.Inhibition of VH-BNST pathway affect both the acquisition,consolidation and retrieval of contextual fear memory.We used optogenetics to inhibit VH-BNST neural circuits during contextual fear memory training and retrieval,then we found that inhibition of VH-BNST affects both the acquisition and retrieval of contextual fear memory,while the mobility of mice is not affected by inhibiting the VH-BNST pathway with optogenetics.We used the DREADD system to selectively silence the VH-BNST pathway after CFC training,and we found that inhibition of VH-BNST affects the consolidation of contextual fear memory.In addition,the mobility of mice is not affected by inhibiting the VH-BNST pathway with chemical genetics.Conclusions:We found there are two different neural circuits from HPC to BNST,DH-BNST and VH-BNST,while these two different pathways participate in different process of contextual fear memory.DH-BNST pathway specifically participate in the retrieval of contextual fear memory,but VH-BNST involved in the acquisition,consolidation and retrieval.In addition,both DH-BNST and VH-BNST pathway don't affect the mobility of mice.