Optogenetic Stimulation Promotes Functional Recovery Of The Lateral Amygdala After Ischemic Stroke At The Level Of Neural Circuits

Recently,stroke has become one of the world’s leading causes of death,and is a serious threat to human health.The incidence of cerebral ischemic stroke(CIS)accounts for 60%～80%of all strokes.CIS is mainly caused by vascular occlusions that lead to poor blood flow.Because CIS is gravely harmful to human health,the focus of both basic and clinical research over the last few decades has been committed to study and produce therapeutic methods to facilitate functional recovery after ischemic stroke.Brain stimulation is one of these methods,and with the advent of optogenetics,a promising method of treatment has arrived,as it can selectively regulate and control the activity of a target area.This study focuses on the functional recovery of the deep brain ischemic stroke with the application of optogenetics in neural circuits.First,we compare ischemia induction in the deep brain lateral amygdala(LA)between an in vivo Endothelin-1(ET-1)injection and the photochemical model.We find that the LA could recover spontaneously from ischemia post-ET-1 injection after 3 days.In contrast,the photochemical method could induce ischemia in the LA for 10 days using a light density of 30mW/mm2 and an illumination time up to 1 hour.This model allows us to study the functional recovery for a long time.The ischemic lateral amygdala affects acquisition of fear conditioning and disrupts retention of tone-conditioned fear,but does not impair retention of contextual fear.These findings suggest that the photochemical method induced in deep brain area leads to functional deficits in learning and memory associated with these regions.We then controlled the activity of the upstream region(AuV),which promoted the functional recovery of the downstream region(LA)with the application of the optogenetic stimulation lasting for two to three days.In conclusion,we made a deep brain ischemic model and regulated the activity of the target area that could help functional recovery after stroke by optogenetics in neural circuits.These findings provide new insight for basic and clinical research which promote functional recovery after ischemia.