All detected genes and differential genes.

An essential function of memory is to guide behavior for better survival and adaptation. While memory formation has been extensively studied, far less is understood about how memory retrieval influences behaviors. In the auditory Pavlovian threat conditioning paradigm using C57BL/6J mice, retrieving a conditioned threat memory is associated with spiking in two dorsomedial prefrontal cortex (dmPFC) neurons with transient (T-neurons) and sustained (S-neurons) patterns. We show here that T-neurons and S-neurons are two distinct neuronal populations with different neuronal and synaptic properties and mRNA profiles. S-neuron spiking matches freezing behavior and is required for freezing. This sustained activity in S-neurons requires auditory inputs and the release of norepinephrine (NE) in the dmPFC. The activation of the locus coeruleus (LC) is initiated by dmPFC T-neuron inputs, sustained by auditory inputs, and is required for the transition to freezing by enhancing S-neuron activity. Interestingly, LC activation precipitates a brief period during which nonconditioned cues also induce freezing. Our findings highlight the critical contribution of the LC/NE system in the transition from memory to behavior, which coordinates the effective integration of memory, sensory inputs and emotional state for optimal adaptation.

记忆的核心功能之一是指导行为，以实现更优的生存与适应。尽管记忆形成已被广泛研究，但人们对记忆提取如何影响行为的认知却极为有限。在采用C57BL/6J小鼠的听觉巴甫洛夫威胁条件反射范式（auditory Pavlovian threat conditioning paradigm）中，条件化威胁记忆的提取，与背内侧前额叶皮层（dorsomedial prefrontal cortex, dmPFC）内两类神经元的锋电位发放相关，二者分别为瞬态型神经元（T-neurons）和持续型神经元（S-neurons）。本研究证实，T神经元与S神经元属于两类截然不同的神经元群，二者在神经元特性、突触属性以及mRNA表达谱上均存在差异。S神经元的锋电位发放与僵住行为（freezing）高度匹配，且是僵住行为产生的必要条件。S神经元的这种持续放电活动，依赖于听觉输入以及背内侧前额叶皮层内去甲肾上腺素（norepinephrine, NE）的释放。蓝斑（locus coeruleus, LC）的激活由dmPFC的T神经元输入触发，并由听觉输入维持，且通过增强S神经元的活动，成为向僵住行为转变的必要环节。值得注意的是，蓝斑的激活会引发一段短暂的窗口期，在此期间非条件化线索也可诱导僵住行为。本研究结果凸显了LC/NE系统在记忆向行为转化过程中的关键作用：该系统可协调记忆、感觉输入与情绪状态的有效整合，以实现最优的适应能力。