Neural Mechanisms Of Obsessive Compulsive-Like Behavior In Mice

BACKGROUND:Obsessive-compulsive disorder (OCD) has become a more and more notable disease in recent years. As growing number of people suffer from OCD,there is still no efficient method to cure the disease. There is still lack of study about the mechanism of OCD, and we don't even have a standard animal model of compulsive behavior. In this study, we tried to build a simple and universal mouse model of compulsive behavior, and further explore the mechanism using the model.METHODS:Chronic injection of dopamine D2 receptor agonist quinpirole can build the mouse compulsive behavior model. Using this model,we conducted a series of immuno histochemistry experiments to confirm which brain areas are involved in the formation of compulsive behavior. We use electrophysiological experiments to check out the activity changes in those areas. And finally,to prove the role of those areas,we conducted a behavior test using optogenetics.RESULTS:(1) Successfully built a mouse compulsive sucrose drinking model; (2) The lateral hypothalamus, the basolateral amygdala and the medial prefrontal cortex are involved in the formation of mouse compulsive behavior; (3) There are neuron projections between the BLA and mPFC; (4) The neurons in BLA-mPFC pathway are glutamate ergic neuron; (5) The neuron activity were increased in BLA glutamate neurons; (6) Stimulating BLA glutamate ergic neurons can induce mouse compulsive behavior.DISCUSSION:We successfully built a simple and universal mouse compulsive sucrose drinking model. Using the mouse model, we confirmed that the glutamate ergic neurons in BLA-mPFC pathway played a role in the formation of mouse compulsive behavior.