Contribution of interneuron types to the emergence of fast network activity patterns in the mouse dentate gyrus

神经网络的节律性活动发生在0.5到300赫兹的不同频率上。在这个广泛的频率范围内，特别是theta- (6-10 Hz)调制的gamma （30-130 Hz）振荡引起了最高的关注，因为它们与编码、存储和通过同步活跃的细胞组件回忆信息的功能关系最为明显。在齿状回中，作为海马体的输入门，theta调制的gamma活动对于人类和啮齿动物的空间导航和获取新的有意识记忆至关重要。在这里，伽马活动模式以两种空间、时间和频谱不同的方式出现，作为30-75 Hz的低伽马，在整个齿状回中发生，以及75-150 Hz的高伽马活动，在空间上受到更多限制（str<s:1> ber等人，2017;Lastoci & Klausberger, 2017）。相反，齿状回的高伽马与其余海马子区没有相位相关，表明它局部局限于齿状回的子网络。这种局部高频伽马活动可能允许对传入信息进行局部处理，并将信息流分离到不重叠的记忆中。因此，局部高伽马活动可能增加齿状回的存储容量。然而，支持在齿状回中产生伽马振荡的电路机制在很大程度上仍然未知。在这里，我们的目标是解决这个基本问题，首先，记录谷氨酸能颗粒细胞（GCs）的动作电位，齿状回的主要细胞，以及gaba能抑制性中间神经元，通过对暴露于虚拟现实的头部固定的非麻醉小鼠齿状回单个细胞进行近细胞记录。其次，我们将在记录期间用染料填充细胞，用于随后的形态学和免疫组织化学鉴定。第三，通过分析单个动作电位与细胞外记录的节律场电位相的时间关系，我们旨在研究不同神经元类型对θ波以及慢速和快速伽马活动模式的贡献差异。我们相信，这项跨学科研究的结果将为啮齿动物齿状回中产生theta调制的gamma振荡的细胞机制提供新的信息，从而提高我们对中间神经元在认知功能中的作用的理解。

Rhythmic activities of neuronal networks occur at various frequencies ranging from 0.5 up to 300 Hz. In this broad frequency range, particularly theta- (6-10 Hz) modulated gamma (30-130 Hz) oscillations attracted highest attention because their functional relationship to coding, storing and recall of information by synchronously active cell assemblies is most evident. In the dentate gyrus, as the input gate of the hippocampus, theta-modulated gamma activity is essential for spatial navigation and acquisition of new conscious memories in humans and rodents. Here, gamma activity patterns emerge in two spatially, temporally and spectrally distinct regimes, as low gamma at 30-75 Hz, occurring globally in the entire dentate gyrus, and as focal more spatially restricted high gamma activities at 75-150 Hz (Strüber et al., 2017; Lastoci & Klausberger, 2017). In contrast, high gamma in the dentate gyrus is not phase correlated to the remaining hippocampal subfields indicating that it is locally restricted to subnetworks of the dentate gyrus. Such local high-frequency gamma activities may allow local processing of incoming information and the segregation of information streams into non-overlapping memories. Thus, local high gamma activity may increase storage capacity of the dentate gyrus. The circuit mechanisms that may support the generation of gamma oscillations in the dentate gyrus remain, however, largely unknown. Here we aim to address this fundamental problem by first, recording action potentials from glutamatergic granule cells (GCs), the principal cells of the dentate gyrus, and GABAergic inhibitory interneurons by performing juxtacellular recordings from individual cells in the dentate gyrus of head-fixed non-anaesthetized mice exposed to a virtual reality. Second, we will fill cells during recording with a dye for subsequent morphological and immunohistochemical identification. Third, by analyzing the temporal relationship of single action potentials to the phases of the extracellularly recorded rhythmic field potentials, we aim to examine differences in the contribution of the various neuron types to theta as well as slow and fast gamma activity patterns. We believe that the results of this interdisciplinary research will provide new information on the cellular mechanisms underlying the generation of theta-modulated gamma oscillations in the rodent dentate gyrus and thereby will improve our understanding on the role of interneurons in cognitive functions.