Theta and respiration: Interactions of two different rhythms in the entrainment of neuronal activity

哺乳动物大脑表达不同类型的网络振荡，这些振荡将神经元带入共同的时间机制。由此产生的时空活动模式被认为是感知、动作、记忆或其他认知行为的神经元表征的基础。存在多种不同类型的振荡，其在频率、潜在机制、空间延伸和与不同功能状态的相关性方面不同。在许多情况下，几种节律共存于同一个局部网络中，有时形成嵌套的快振荡和慢振荡。目前还不清楚单个神经元是如何受到这种复杂模式的影响的，我们想研究最近发现的两种不同振荡之间的相互作用，这两种振荡覆盖了小鼠大脑中强烈重叠的频带：θ振荡（4-12 Hz）和呼吸相关节律（RR，2-12 Hz）。在过去的几年里，我们和其他人已经证明，与呼吸相关的网络振荡会在多个大脑区域中携带神经元，远远超出了特定的呼吸或嗅觉网络。在这些区域中的许多区域，例如顶叶和额叶皮层或海马，我们同时观察到θ振荡和RR振荡。这一发现指向自主产生的节律（theta）和感觉反馈（RR）之间的相互作用。我们想分析这个有趣的模型系统之间的相互作用不同的振荡制度，问三个基本问题：1。共存的theta和RR如何影响多神经元活动模式？2.神经元夹带的机制是什么？这两种节律之间有什么不同？3. (How)非突触（“远场”）机制影响皮层网络中的多神经元模式吗？我们将在体内和体外应用多种电生理学方法，包括四极记录，多电极阵列，高分辨率并列和细胞内技术和先进的分析方法。神经元活动的刺激包括体内光遗传学方法和体外脑切片中的外部AC电位。总之，我们的实验将阐明复杂神经元活动模式产生的新机制。与此同时，我们希望阐明感觉（呼吸/嗅觉）反馈对小鼠大脑中广泛活动模式的影响。

The mammalian brain expresses different types of network oscillations which entrain neurons into a common temporal regime. The resulting spatio-temporal activity patterns are believed to underlie neuronal representations of perceptions, actions, memories or other cognitive acts. There are multiple different types of oscillations which vary in frequency, underlying mechanisms, spatial extension and correlation with different functional states. In many cases, several rhythms co-exist in the same local network, sometimes forming nested fast and slow oscillations. It is far from clear how individual neurons are affected by such complex patterns.We want to study a recently discovered interaction between two different oscillations which cover strongly overlapping frequency bands in the mouse brain: theta oscillations (4-12 Hz) and respiration-related rhythms (RR, 2-12 Hz). During past years, we and others have shown that respiration-related network oscillations entrain neurons in multiple brain regions, far beyond specific respiratory or olfactory networks. In many of these areas, e.g. the parietal and frontal cortex or the hippocampus, we observe theta- and RR-oscillations at the same time. This finding points towards an interaction between autonomously generated rhythms (theta) and sensory feedback (RR). We want to analyze this interesting model system for interactions between different oscillatory regimes, asking three fundamental questions:1. How do co-existing theta and RR affect multi-neuronal activity patterns?2. What are the mechanisms of neuronal entrainment, and do these differ between both rhythms?3. (How) do non-synaptic (`far field´) mechanisms affect multi-neuronal patterns in cortical networks?We will apply multiple electrophysiological methods in vivo and in vitro, including tetrode recordings, multi-electrode arrays, high-resolution juxta-and intracellular techniques and advanced methods of analysis. Stimulation of neuronal activity includes optogenetic approaches in vivo and external AC-potentials in brain slices in vitro. Together, our experiments shall elucidate new mechanisms underlying the generation of complex neuronal activity patterns. At the same time, we want to shed light on the impact of sensory (respiratory/olfactory) feedback on widespread activity patterns in the murine brain.