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Linking birthdate with functional diversity in CA1 pyramidal neurons in the awake mouse hippocampus

将出生日期与清醒小鼠海马 CA1 锥体神经元的功能多样性联系起来

基本信息

批准号：
254966771
负责人：
Dr. Susanne Reichinnek
金额：
--
依托单位：
Institut de Neurobiologie (INMED)
依托单位国家：
德国
项目类别：
Research Fellowships
财政年份：
2014
资助国家：
德国
起止时间：
2013-12-31 至 2015-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/254966771?language=en
关键词：
Linking birthdate functional diversity CA1

项目摘要

Cell type diversity classically reflects the available repertoire of neuronal functions in different brain regions. The hippocampus processes multimodal information and is important for spatial and declarative memory function. During spatial exploration, principal cells of all hippocampal subfields are entrained by a theta-nested gamma oscillation, forming transient assemblies of co-active neurons (Buzsaki and Draguhn 2004). These co-active neurons form sequential activation patterns which finally represent the animal´s trajectory through space (OKeefe and Reece 1993). During sleep these sequences are re-activated for consolidation purposes by sharp-wave ripple oscillations (Wilson 1994) . The organization of neuronal assemblies requires a structuring element. Different cell types probably entrain neuronal groups, coordinate state-dependent oscillations and therefore structure the various network functions. So far, cell diversity in the hippocampus seems to be a major hallmark for GABAergic cells (Klausberger 2008). Their activity was shown to be correlated to different network states and is partly rooted in their spatio-temporal embryonic origin. In contrast, only few studies address the possibility that glutamatergic CA1 pyramidal cells may comprise several subtypes with different genetic, morphological and functional features although they represent 80% of the neuronal population. In addition, the Cossart lab has found that an early temporal origin delineates a distinct morpho-functional subtype of glutamatergic neuron in the CA3 region of the hippocampus (Marissal 2012) in vitro.My project aims to understand the relationship between developmental fate and neuronal network dynamics of hippocampal glutamatergic neurons in the hippocampal subfield CA1. My project is based on a transgenic mouse line from the Cossart group (Allene 2012) where the transcription factor Neurogenin2 (Ngn2) permits the labeling of glutamatergic neurons according to their birthdate. I will perform electrophysiological recordings in acute hippocampal slices to characterize basic electrophysiological properties of early-born (embryonic day 11) and late-born (embryonic day 15) neurons in CA1. In addition, I want to determine physiological activity patterns of these cells in awake mice running on a treadmill. Using 2-photon calcium imaging, a stereotactically delivered, genetically-encoded calcium indicator (GCaMP-6) will indicate single action potentials within a single focal plane of the dorsal CA1 subfield. Thereby, I will monitor firing pattern of several pyramidal cells during typical behaviorally-relevant network oscillations (exploration - theta-nested gamma and waking immobility/sleep - sharp wave ripple) and investigate their recruitment into network oscillations.The results will provide important insights into how developmental fate affects network recruitment and network dynamics.

细胞类型多样性通常反映了不同大脑区域神经元功能的可用库。海马体处理多模式信息，对于空间和陈述性记忆功能很重要。在空间探索过程中，所有海马亚区的主要细胞都受到 θ 嵌套伽玛振荡的影响，形成协同活动神经元的瞬时集合（Buzsaki 和 Draguhn 2004）。这些共同活动的神经元形成顺序激活模式，最终代表动物在空间中的轨迹（OKeefe 和 Reece 1993）。在睡眠期间，这些序列通过尖波纹波振荡重新激活以达到巩固的目的（Wilson 1994）。神经元集合的组织需要结构元素。不同的细胞类型可能夹带神经元群，协调状态依赖性振荡，从而构建各种网络功能。到目前为止，海马体的细胞多样性似乎是 GABA 能细胞的主要标志 (Klausberger 2008)。它们的活动被证明与不同的网络状态相关，并且部分根源于它们的时空胚胎起源。相比之下，只有少数研究表明谷氨酸能 CA1 锥体细胞可能包含具有不同遗传、形态和功能特征的几种亚型，尽管它们代表了神经元群体的 80%。此外，Cossart 实验室在体外发现，早期时间起源描绘了海马 CA3 区域谷氨酸能神经元的独特形态功能亚型（Marissal 2012）。我的项目旨在了解海马 CA1 亚区海马谷氨酸能神经元的发育命运与神经元网络动态之间的关系。我的项目基于 Cossart 小组 (Allene 2012) 的转基因小鼠品系，其中转录因子 Neurogenin2 (Ngn2) 允许根据谷氨酸能神经元的出生日期对其进行标记。我将在急性海马切片中进行电生理记录，以表征 CA1 中早产（胚胎第 11 天）和晚产（胚胎第 15 天）神经元的基本电生理特性。此外，我想确定在跑步机上跑步的清醒小鼠中这些细胞的生理活动模式。使用 2 光子钙成像，立体定向递送的基因编码钙指示剂 (GCaMP-6) 将指示背侧 CA1 子场的单个焦平面内的单个动作电位。因此，我将监测典型的行为相关网络振荡期间几个锥体细胞的放电模式（探索 - θ嵌套伽马和清醒不动/睡眠 - 尖锐波波纹），并研究它们对网络振荡的招募。结果将为发育命运如何影响网络招募和网络动态提供重要见解。