Assessment of olfaction-controlled developmental time windows with critical function for adult cognitive abilities

虽然感觉加工和认知加工的发展原理已经被广泛研究，但它们之间的协同作用仍然在很大程度上被忽视。电活动的协调模式，无论是由内源性产生的，还是由感觉输入驱动的，都塑造了在分子线索影响下出现的神经电路的支架。特别是在关键时期，感觉回路受到经验的调节。同样，负责认知处理的复杂边缘回路，包括前额叶皮质(PFC)、海马体(HP)、丘脑核团和外侧内嗅皮层(LEC)，都通过β-β带振荡活动进行精炼。最近，我们提供了第一批来自小鼠的实验数据，这些数据支持边缘发育存在临界期。在这个早期，大多数感官系统还不成熟(啮齿动物是盲人、聋人，不会胡须)，嗅觉提供了环境输入的主要来源，对生存至关重要。在之前的DFG资助的支持下，我们证明了在新生小鼠的嗅球(OB)中自发产生或气味诱导的电活动模式通过单突触和多突触投射激活LEC，进而促进HP到PFC的通讯。我们认为，在新生儿发育的特定时间窗(S)中，OB的激活对成人LEC-HP-PFC回路的功能和认知表现至关重要。为了解决这一假设，多点记录将与体内的光和化学遗传学以及行为测试相结合。首先，我们将监测在新生儿发育的特定时间窗(S)内，短暂操作OB活动后，LEC-HP-PFC回路的成熟动力学和成人功能。其次，在上述OB操作后，将测试成人的认知绩效(再认和工作记忆、决策)。最后，我们将评估早期气味暴露对成人认知能力和“丢失”婴儿记忆(“普鲁斯特现象”)恢复的影响。这些研究将机械地阐明认知能力如何依赖于早期的感觉印记。

Although the developmental principles of sensory and cognitive processing have been extensively investigated, their synergy is still largely neglected. Coordinated patterns of electrical activity, either endogenously generated or driven by sensory inputs, shape the scaffold of neural circuitry emerged under the influence of molecular cues. Especially during the critical periods, the sensory circuits are modulated by experience. Similarly, the complex limbic circuits accounting for cognitive processing that include the prefrontal cortex (PFC), hippocampus (HP), thalamic nuclei, and lateral entorhinal cortex (LEC), are refined by theta-beta band oscillatory activity. Recently, we provide first experimental data from mice that support the presence of critical periods for limbic development. At this early age, when most sensory systems are still immature (rodents are blind, deaf and do not whisker), the sense of olfaction provides the main source of environmental inputs, being critical for survival. Supported by a previous DFG grant, we demonstrated that spontaneously generated or odor-induced patterns of electrical activity in the olfactory bulb (OB) of neonatal mice activate the LEC via mono- and polysynaptic projections that, on its turn, boosts the HP-to-PFC communication. Here, we propose that activation of OB during defined time window(s) of neonatal development is critical for the adult function of LEC-HP-PFC circuits and cognitive performance. To address this hypothesis, multi-site recordings will be combined with opto- and chemogenetics in vivo as well as behavioral testing. First, the maturational dynamics and adult function of LEC-HP-PFC circuits after transient manipulation of OB activity during defined time window(s) of neonatal development will be monitored. Second, the adult cognitive performance recognition and working memory, decision making) will be tested after the OB manipulation described above. Finally, the impact of early odor exposure on adult cognitive abilities and recovery of “lost” infant memories (“Proust phenomenon”) will be assessed. The investigations will mechanistically elucidate how cognitive performance relies on early sensory imprinting.