Development, plasticity and ensemble recruitment of AcD cells in the hippocampus

海马 AcD 细胞的发育、可塑性和整体招募

• 批准号: 427956063
• 负责人: Privatdozent Dr. Martin Both
• 金额: --
• 依托单位: Lehrstuhl Neuroanatomie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/427956063?language=en
• 关键词: Development; plasticity; ensemble; recruitment; AcD

The hippocampus is important for the formation of episodic and semantic memory. To achieve this, it generates distinct network oscillations, during which groups of neurons – functional ensembles – are activated specifically. This activation has the following principle: dendritic excitatory synaptic potentials that remain below threshold to elicit an action potential (AP) are integrated at the soma and directed towards the axon, which emanates at the soma. At the axon initial segment, an AP is then generated. At various points along this pathway, inhibitory signals may elicit constrain on this integration. Of particular interest is perisomatic inhibition that targets the soma specifically.Recently, we showed that in about 50 % of principal neurons, the morphology of axon onset deviates from the above mentioned principle (axon at soma). Instead, the axon emerges off a basal dendrite. This basal dendrite is more effective in converting excitatory potentials into APs than other dendrites. In addition, this morphological phenotype may have another consequence at the network level: excitatory potentials at the axon-carrying dendrite can elicit APs by circumventing perisomatic inhibition, while all other incoming signals are attenuated significantly. We already verified this hypothesis in an in vitro model of network oscillations. Now, we plan to investigate if the morphological differences between neurons allow for a novel and fundamental mechanism, which controls the integration and propagation of information via perisomatic inhibition. This is relevant since different states of consciousness, e.g. the retrieval of memories, depends on specific network rhythms, which recruit distinct inhibition. In this context, it is important to understand when and how these specific neurons are developed (for example via genetic programs or possibly by brain activation patterns in a self-regulatory manner). Finally, we want to study whether morphologically distinct neurons are integrated into the existing network differently. Do they have different presynaptic partners or postsynaptic targets? Is their local connectivity, particularly with inhibitory neurons, different?In summary, we aim at investing how cellular mechanisms and morphologies contribute to regulate functional ensembles in dependence of the conscious state. In this context, neurons with axon-carrying dendrites might represent a privileged group of cells with hitherto unknown functions.

海马体对于情景记忆和语义记忆的形成非常重要。为了实现这一点，它产生了独特的网络振荡，在此期间，神经元组-功能集合-被特定地激活。这种激活具有以下原理：保持低于阈值以引发动作电位（AP）的树突兴奋性突触电位在索马处被整合并指向轴突，轴突在索马处发出。在轴突初始段，然后生成AP。在沿着该途径的不同点，抑制信号可能引起对该整合的限制。特别令人感兴趣的是特异性靶向索马的体周抑制。最近，我们发现在大约50%的主神经元中，轴突起始的形态偏离了上述原则（轴突在索马）。相反，轴突从基底树突上长出来。这种基底树突在将兴奋电位转化为AP方面比其他树突更有效。此外，这种形态表型可能在网络水平上产生另一个后果：轴突携带树突的兴奋电位可以通过绕过体周抑制来引发AP，而所有其他传入信号都显着衰减。我们已经在体外网络振荡模型中验证了这一假设。现在，我们计划研究神经元之间的形态差异是否允许一种新的基本机制，该机制通过体周抑制控制信息的整合和传播。这是相关的，因为不同的意识状态，例如记忆的检索，取决于特定的网络节奏，这招募了不同的抑制。在这种情况下，重要的是要了解这些特定的神经元是何时以及如何发育的（例如通过遗传程序或可能通过自我调节方式的大脑激活模式）。最后，我们想研究形态上不同的神经元是否以不同的方式整合到现有的网络中。它们有不同的突触前伴侣或突触后靶点吗？它们的局部连接，特别是与抑制性神经元的连接，是否不同？总之，我们的目标是研究细胞机制和形态如何有助于调节依赖于意识状态的功能合奏。在这种情况下，带有轴突树突的神经元可能代表了一组具有迄今未知功能的特权细胞。