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

尽管感觉和认知加工的发展原理已被广泛研究，但它们的协同作用仍在很大程度上被忽视。协调的电活动模式，无论是内源性产生的还是由感觉输入驱动的，在分子线索的影响下形成了神经回路的支架。特别是在关键时期，感觉回路受到经验的调节。同样，包括前额叶皮层（PFC）、海马体（HP）、丘脑核和外侧内嗅皮层（LEC）在内的复杂边缘回路负责认知处理，它们通过θ - β波段振荡活动得到完善。最近，我们提供了第一个来自小鼠的实验数据，支持边缘发育的关键时期的存在。在这个早期阶段，大多数感觉系统还不成熟（啮齿动物是盲的，聋的，没有胡须），嗅觉提供了环境输入的主要来源，对生存至关重要。在先前DFG资助的支持下，我们证明了新生小鼠嗅球（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 - pfc通信。在此，我们提出，在新生儿发育的特定时间窗内，OB的激活对成年后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，多位点记录将与体内光遗传学和化学遗传学以及行为测试相结合。首先，在新生儿发育的定义时间窗内，对OB活动进行短暂操纵后，将监测LEC-HP-PFC回路的成熟动态和成人功能。其次，在上述OB操作后，对成人的认知表现（认知和工作记忆，决策）进行测试。最后，将评估早期气味暴露对成人认知能力和“丢失”的婴儿记忆恢复的影响（“普鲁斯特现象”）。这些研究将从机制上阐明认知表现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.