Mechanisms Of The Hippocampal-Hypothalamic Circuit In Regulation Of Instinctive Emotion

Dorsomedial hypothalamic nucleus(DMH)is an important component of autonomic nervous system and the regulatory center of visceral activity,which directly or indirectly stimulates pituitary activity to control viscera and endocrine glands,and regulates important physiological functions such as body temperature,feeding,water balance,endocrine,heart rate and blood pressure.Any injury in hypothalamus may cause disorders and abnormalities of physiological activities,accompanied with abnormal emotional and mental reactions.When instinctive emotions such as anxiety and fear,animals often have physiological reactions such as elevated blood pressure,accelerated heart rate and breathing frequency.Meanwhile,DMH has extensive connections with limbic system that may participates in the regulation of instinctive emotions such as anxiety and fear,however,the cellular mechanisms are largely unknown.In this study,the glutamatergic neurons and gamma-aminobutyric acid(GABAergic)neurons in local DMH and v SUB(Ventromedial Subiculum)-DMH circuit of mice were specifically regulated by optogenetics.The changes of anxiety and fear were assessed by animal behavioral studies such as predator fear test,elevated plus maze test,open field test and heart rate test.We found that activation of glutamatergic and GABAergic neurons in DMH and v SUB-DMH circuit can significantly induce anxiety and fear-like behaviors,and increase heart rate,while optical inhibition of both neurons significantly suppressed anxiety and fear-like behaviors,and decreased heart rate.Our findings confirms the bi-directional regulation of anxiety and fear by specific types of neurons in local DMH and v SUB-DMH circuit,and may provide new targets for clinical intervention of neuropsychiatric disorders.