Dissection Of Hippocampal-lateral Septal Circuit In Regulating Innate Behaviors

Nowadays,the global medical burden of neuropsychiatric disorders accounts for13% of all diseases,which is on the top of the list.Epilepsy is a common nervous system disease,which has always been concerned by people because of the unpredictably intermittent seizures,high rates of psychiatric comorbidities,and increased premature mortality.The probable cause that epileptics have a high risk of accidental death is that epileptic seizures damage specific neural circuits which may be involved in environmental cue processing and defensive behavior.However,the hippocampus is the most vulnerable brain region in epilepsy.The hippocampus is thought to be involved in environmental exploration and cognitive processes under physiological condition.The lateral septum is one of the two major outputs of hippocampus,which strongly project to the hypothalamus,amygdala and other subcortical brain regions.The hippocampal-lateral septal circuit is likely to be involved in the regulation between the processing of environmental cues and the defense behavior,however,its circuit mechanism has not been clarified yet.In order to investigate the aforesaid hypothesis,we developed a tool based on optogenetics and electrophysiology,a drivable microwire electrode array.The result of the evaluation of the performance of the electrode showed that it can be implanted and driven in hippocampus and lateral septum independently.Furthermore,the electrode is suitable for multiple brain regions behavior and electrophysiology recording due to the small size,light weight,strong anti-interference capability,and long-term recording stability.The electrode is a reliable tool for modulating and dissecting neural circuits based on optogenetics and and electrophysiology.To investigate the circuit mechanism of epilepsy induced abnormal defense behavior,unilateral intra-hippocampus injection of kainic acid was adopted to obtain the epileptic mice model,which showed similar phenotype with epilepsy in behavioral,electrophysiology,and histology.Predator threat test was applied to evaluate the defensive behavior of mice,and the results showed that epileptic mice exhibited decreased defensive behavior to predators.Electrophysiological data analysis suggested that the hippocampal-lateral septal circuit is involved in the regulation between environmental cues and defensive behavior through θ and α oscillations.In conclusion,the newly developed drivable microwire electrode array is suitable for multiple brain regions simultaneous recording,and it is beneficial to the dissection of neural circuits coupled with optogenetics.The θ oscillations in hippocampal-lateral septal circuit involved in modulation of defensive behavior,and the abnormal θoscillations in the pathway of epileptic mice induced abnormal defensive behavior.The investigation of the hippocampal-lateral septal circuit in abnormal defensive behavior of epileptic mice is of great importance of understanding the cause of increased accidental mortality of epilepsy patients and seeking potential targets for intervention.