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

海马体对情景记忆和语义记忆的形成很重要。为了实现这一目标，它产生了不同的网络振荡，在此期间，神经元群（功能集合）被特异性地激活。这种激活有以下原理：树突兴奋性突触电位保持在触发动作电位（AP）的阈值以下，在体细胞整合并定向到轴突，轴突在体细胞发出。在轴突初始段产生AP。在这条通路的不同点上，抑制信号可能会对这种整合产生约束。特别令人感兴趣的是特异性针对体细胞的细胞周围抑制。最近，我们发现在大约50%的主神经元中，轴突的形态偏离了上述原则（轴突位于体细胞）。相反，轴突从基生树突上出现。基底树突比其他树突更能有效地将兴奋电位转化为ap。此外，这种形态表型可能在网络水平上产生另一种结果：携带轴突的树突的兴奋电位可以通过绕过细胞周围抑制而引发ap，而所有其他传入信号都显着减弱。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和基本的机制，通过细胞周围抑制来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，这需要不同的抑制。在这种情况下，了解这些特定神经元何时以及如何发育是很重要的（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伙伴或突触后目标吗？它们的局部连通性，尤其是与抑制性神经元的连通性不同吗？总之，我们的目标是投资细胞机制和形态如何有助于调节依赖于意识状态的功能集合。在这种情况下，具有轴突携带树突的神经元可能代表了一组迄今为止未知功能的特权细胞。

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.