Prefrontal dynamics and encoding of flexible rule switching.
Prefrontal dynamics and encoding of flexible rule switching.
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灵活规则切换的前额动力学和编码。
DOI：
10.1101/2023.12.13.571356
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Yang,Hongdian
中科院分区：
文献类型：
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作者：
Nigro,Marco;Tortorelli,LucasSilva;Dinh,Kevin;Garad,Machhindra;Zlebnik,NatalieE;Yang,Hongdian
行为灵活性，即调整行为策略以应对不断变化的环境突发事件和内部需求的能力，是认知功能的基础。尽管有大量的药理学和损伤研究，但支持灵活规则转换的潜在神经生理学相关性和机制正在积极研究中。为了解决这个问题，我们训练小鼠区分复杂的感官线索，包括不同的感知维度（集转移）。内镜钙成像显示，内侧前额叶皮层（mPFC）神经元表现出明显的动态变化，在规则切换。值得注意的是，突出的编码能力，在mPFC与切换，但不是在感知维度。然后，我们显示了从蓝斑（LC）的上行输入的功能的重要性，LC抑制受损的规则切换行为，阻碍mPFC的动态过程和编码。我们的研究结果强调了mPFC在设置转换过程中的关键作用，并展示了上行神经调节对塑造前额叶神经动力学和行为灵活性的深远影响。
Behavioral flexibility, the ability to adjust behavioral strategies in response to changing environmental contingencies and internal demands, is fundamental to cognitive functions. Despite a large body of pharmacology and lesion studies, the underlying neurophysiological correlates and mechanisms that support flexible rule switching are under active investigation. To address this question, we trained mice to distinguish complex sensory cues comprising different perceptual dimensions (set shifting). Endoscopic calcium imaging revealed that medial prefrontal cortex (mPFC) neurons exhibited pronounced dynamic changes during rule switching. Notably, prominent encoding capacity in the mPFC was associated with switching across, but not within perceptual dimensions. We then showed the functional importance of the ascending input from the locus coeruleus (LC), as LC inhibition impaired rule switching behavior and impeded mPFC dynamic processes and encoding. Our results highlight the pivotal role of the mPFC in set shifting processes and demonstrate the profound impact of ascending neuromodulation on shaping prefrontal neural dynamics and behavioral flexibility.