Effects Of Chronic Stress On Morphology And Density Of Presynaptic Boutons In Reciprocal Projection Neurons Of Brain Regions In The Affective Circuit

Presynaptic bouton is a kind of irregular spherical specialized structure distributed axonal fiber terminals,which contains a large number of neurotransmitters enclosed in synaptic vesicles as well as some organelles,such as mitochondria and endoplasmic reticulum.As the key component of the presynaptic structure,bouton directly controls the release of neurotransmitters and forms functional synapses through contact with the postsynaptic membrane.Numbers of studies have revealed that the structure of presynaptic bouton is highly dynamic in a variety of physiological and pathological processes,and these structural dynamic changes of bouton are considered to contribute to the synaptic plasticity.Stress refers to a series of non-specific responses of organisms to adverse environmental or psychological stimuli,which can help organisms quickly adjust their state to deal with emergencies in the face of danger.This is critical for the survival of organisms.However,suffering persistent stress leads to maladaptive responses in central nervous system.A large number of studies have shown that the pathogenesis of a variety of neuropsychiatric diseases,including mood and anxiety disorders,is closely related to the maladaptive responses caused by chronic stress in the brain.These maladaptive responses include changes in the structure and function of synapse in multiple brain regions of the affective circuit,but most of the researches were only focused on the changes of dendrites and spines.Little is known when it comes to the structural changes of presynaptic bouton after chronic stress exposure and the functional significance of such changes. To illuminate the effects of chronic stress on presynaptic boutons in reciprocal projection neurons of each brain regions in the affective circuit,AAV_2-8-Ca MKII?-m Cherry virus was injected into mPFC,vHPC and BLA to label the local projection neurons?PNs?and trace the projection fibers in target downstream brain regions,then reconstruct the axon terminals and measure the morphology and density of boutons,at last electrophysiology tests were carried out in these neural circuits whose presynaptic bouton changes after stress exposure to explore whether these bouton morphological changes were accompanied by synaptic functional alteration.The results revealed that:1.Chronic stress decreased the size and density of bouton in the axon terminals of mPFC PNs targeting BLA?mPFC?BLA?,and the effects were restricted in the axon terminals of mPFC PNs targeting rostral BLA?mPFC?rostral BLA?;in stressed mice,boutons in the the axon terminals of vHPC?caudal BLA PNs showed lower density than the control ones,but the size and density of whole boutons in the the axon terminals of vHPC?BLA PNs wasn't influenced by chronic stress at all;as for the boutons in the axon terminals of vHPC?mPFC PNs,the density was unaltered,whereas the boutons in the axon terminals of vHPC?IL PNs showed size atrophy after stress exposure.2.Chronic stress increased the density of bouton in the axon terminals of BLA?vHPC PNs,meanwhile boutons in the axon terminals of BLA?PL and BLA?IL PNs showed the same change patterns,in addition to this,chronic stress increased the size of the boutons in the axon terminals of BLA?IL PNs.3.Chronic stress significantly increased the release of glutamate in mPFC?BLA?BLA?vHPC?BLA?PL and BLA?IL these four neural circuits.In conclusion,in the reciprocal projection circuits among mPFC?vHPC and BLA,chronic stress can induce changes in morphology and density of presynaptic bouton,and these effects showed circuit preference.Meanwhile,in all these circuits whose presynaptic bouton changes after stress exposure also showed synaptic functional alteration.