Parvalbumin-Expressing Neurons Network Plasticity and Fear Extinction

【摘要】 Learning to fear threats in the environment is highly adaptive. However,this form of learning can also lead to pathological fear memories that fuel disorders of fear and anxiety,such as panic disorder and post-traumatic stress disorder(PTSD) in humans. Increasing evidence suggests that the ventral medial prefrontal cortex(vmPFC) is involved in fear extinction. However,no studies have as yet addressed the local network plasticity in fear extinction. Here,we studied the role of parvalbumin(PV) neurons network plasticity in the extinction of cued fear memory and the underlying molecular mechanisms. vmPFC is composed of prelimbic cortex(PL) and infrelimbic cortex(IL). We provide evidence that fear extinction induced a low PV-network configuration in IL cortex but not in PL cortex and this kind of configurationis essential for the extinction.Moreover,by screening an amount of molecules that are known to regulate GABAergic neuronal development,we identified that NRG1-ErbB4 signaling in PV neurons was critical to regulating fear extinction via modulation of PV-networks plasticity. Our study suggests that this signaling may be a potential target for the treatment of fear-related diseases.更多还原

【Abstract】 Learning to fear threats in the environment is highly adaptive. However,this form of learning can also lead to pathological fear memories that fuel disorders of fear and anxiety,such as panic disorder and post-traumatic stress disorder(PTSD) in humans. Increasing evidence suggests that the ventral medial prefrontal cortex(vmPFC) is involved in fear extinction. However,no studies have as yet addressed the local network plasticity in fear extinction. Here,we studied the role of parvalbumin(PV) neurons network plasticity in the extinction of cued fear memory and the underlying molecular mechanisms. vmPFC is composed of prelimbic cortex(PL) and infrelimbic cortex(IL). We provide evidence that fear extinction induced a low PV-network configuration in IL cortex but not in PL cortex and this kind of configurationis essential for the extinction.Moreover,by screening an amount of molecules that are known to regulate GABAergic neuronal development,we identified that NRG1-ErbB4 signaling in PV neurons was critical to regulating fear extinction via modulation of PV-networks plasticity. Our study suggests that this signaling may be a potential target for the treatment of fear-related diseases.更多还原