【2022 學術演講】Mechanisms underlying impulsive aggression : from synapse, neural circuits to the behavior

2022 神醫中心學術演講 4 (現場+視訊) 

日期 : 4月 26日星期二

時間 : 上午11:00  

地點 : 國衛院竹南院區/ 行政大樓B1第6會議室 

主題 : Mechanisms underlying impulsive aggression :

from synapse, neural circuits to the behavior

講師 : 簡伯武  院長 

成功大學生物科學與科技學院

報名連結


視訊系統 Webex  : 會議連結     密碼: 1234

摘要

Dysfunction in emotional quotient is a core symptom of intermittent explosive disorder. The patients are incapable of restraining behaviors and often show outbursts of rage and violent acts, thus endangering personal relationship and provoking social instability. However, the neural mechanisms that provoke impulsive aggression and its regulation are poorly understood. Here we show in mice that modulation of the release of serotonin (5-HT) from dorsal raphe neurons in the ventral hippocampus (vHip) alleviates aggressive behavior. AAV5-hSyn-hM3D(Gq)-mCherry was transfected to the dorsal raphe nuclei (DRN) and CNO was infused to the ventral hippocampus (vHip) of socially isolated (SI) mice. CNO treatment reduced the stress-provoked attack behavior in hM4D(Gq)-expressing mice and the effect was abolished by serotonin 1B receptor (5-HT1BR) antagonist SB-224289. In addition, c-Fos expression in the vHip markedly decreased in the CNOinjected mice indicating that activation of DRN effectively inhibits neural activity of the vHip. Retrograde AAVrg-hSyn-hM3D(Gq)-mCherry was bilaterally transduced to the vHip and cannulas were implanted in the DRN. Infusion of CNO to the DRN resulted in an inhibition of stressprovoked attack behavior that could be abolished by SB-224289. Conversely, activation of median raphe nuclei (MRN)-vHip pathway failed to affect stress-provoked c-Fos expression in the vHip and attack behavior. The stress-provoked attack behavior was inhibited by 5-HT1BR agonists anpirtoline or CP-93129. Pre-treatment with SB-224289 blocked the response of SI mice to CP-93129. Antiaggressive effect of CP-93129 retained following p-chlorophenylalanine (PCPA)-induced 5-HT depletion. These results suggest that the DRN-vHip pathway is critical for the regulation of attack behavior and targeting 5-HT1BR could be a new strategy for treating aggression symptom such as intermittent explosive disorder.



更新 : 2022-04-30

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