前额叶抑制驱动概率性条件恐惧形成和动态表达。
Prefrontal inhibition drives formation and dynamic expression of probabilistic Pavlovian fear conditioning.
机构信息
State Key Laboratory of Chemical Oncogenomics, Guangdong Provincial Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen 518055, PRC.
State Key Laboratory of Chemical Oncogenomics, Guangdong Provincial Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen 518055, PRC.
出版信息
Cell Rep. 2021 Aug 10;36(6):109503. doi: 10.1016/j.celrep.2021.109503.
The association between cause and effect is usually probabilistic. Memories triggered by ambiguous cues may be altered or biased into a more negative perception in psychiatric diseases. Understanding the formation and modulation of this probabilistic association is important for revealing the nature of aversive memory and alterations in brain diseases. We found that 50% conditioned and unconditioned stimuli (CS-US) association during Pavlovian fear conditioning results in reduced fear responses and neural spiking in the dorsomedial prefrontal cortex (dmPFC) due to enhanced inhibition from dmPFC parvalbumin (PV) neurons. Formation of probabilistic memory is associated with increased synaptic inputs to PV-neurons and requires activation of ventral hippocampus, which detects CS-US mismatch during conditioning. Stress prior to conditioning impairs the formation of probabilistic memory by abolishing PV-neuronal plasticity, while stress prior to memory retrieval reverts enhanced PV-neuron activity. In conclusion, PV-neurons tailor learned responses to fit brain state at the moment of retrieval.
因果关系通常是概率性的。在精神疾病中,由模棱两可的线索触发的记忆可能会被改变或偏向于更消极的感知。了解这种概率关联的形成和调节对于揭示厌恶记忆的本质和大脑疾病的改变非常重要。我们发现,在条件性恐惧条件反射过程中,50%的条件和非条件刺激(CS-US)关联会导致背内侧前额叶皮层(dmPFC)中的恐惧反应和神经放电减少,这是由于 dmPFC 中 parvalbumin(PV)神经元的抑制增强所致。概率记忆的形成与 PV 神经元的突触输入增加有关,需要腹侧海马体的激活,该海马体在条件反射过程中检测 CS-US 不匹配。在条件反射之前的应激会通过消除 PV 神经元的可塑性来破坏概率记忆的形成,而在记忆检索之前的应激会使增强的 PV 神经元活动恢复正常。总之,PV 神经元根据检索时刻的大脑状态调整学习反应。