Determining biophysical details of spatially extended neurons is a challenge that needs to be overcome if we are to understand the dynamics of brain function from cellular perspectives. Moreover, we now know that we should not average across recordings from many cells of a given cell type to obtain quantitative measures such as conductance since measures can vary multiple-fold for a given cell type. In this work we examine whether a tight combination of experimental and computational work can address this challenge. The oriens-lacunosum/moleculare (OLM) interneuron operates as a “gate” that controls incoming sensory and ongoing contextual information in the CA1 of the hippocampus, making it essential to understand how its biophysical properties contribute to memory function. OLM cells fire phase-locked to the prominent hippocampal theta rhythms, and we previously used computational models to show that OLM cells exhibit high or low theta spiking resonance frequencies that depend respectively on whether their dendrites have hyperpolarization-activated cation channels (h-channels) or not. However, whether OLM cells actually possess dendritic h-channels is unknown at present. We performed a set of whole-cell recordings of OLM cells from mouse hippocampus and constructed three multi-compartment models using morphological and electrophysiological parameters extracted from the same OLM cell, including per-cell pharmacologically isolated h-channel currents. We found that the models best matched experiments when h-channels were present in the dendrites of each of the three model cells created. This strongly suggests that h-channels must be present in OLM cell dendrites and are not localized to their somata. Importantly, this work shows that a tight integration of model and experiment can help tackle the challenge of characterizing biophysical details and distributions in spatially extended neurons. Full spiking models were built for two of the OLM cells, matching their current clamp cell-specific electrophysiological recordings. Overall, our work presents a technical advancement in modeling OLM cells. Our models are available to the community to use to gain insight into cellular dynamics underlying hippocampal function.

如果要从细胞角度了解脑功能的动态变化，确定空间扩展神经元的生物物理细节是一个必须克服的挑战。而且，我们现在知道，我们不应该对给定细胞类型的许多细胞的记录进行平均，以获得诸如电导之类的定量指标，因为对于给定细胞类型，指标可能会发生多种变化。在这项工作中，我们研究了将实验工作和计算工作紧密结合是否可以应对这一挑战。Oriens-Launosum / Molecularculare（OLM）interneuron作为“门”，控制海马CA1中传入的感觉和正在进行的情境信息，因此必须了解其生物物理特性如何促进记忆功能。OLM细胞被锁定在突出的海马theta节律上，并且我们以前使用计算模型来显示OLM细胞表现出高或低的theta峰值共振频率，这分别取决于它们的树突是否具有超极化激活的阳离子通道（h通道）。但是，目前尚不清楚OLM细胞是否真正具有树突状h通道。我们对小鼠海马中的OLM细胞进行了全细胞记录，并使用从同一OLM细胞中提取的形态和电生理参数（包括每细胞药理学分离的h通道电流）构建了三个多室模型。我们发现，当在创建的三个模型细胞的每个树突中都存在h通道时，这些模型与实验最匹配。这有力地暗示了H通道必须存在于OLM细胞树突中并且不局限于其躯体。重要的是，这项工作表明模型与实验的紧密结合可以帮助解决表征空间扩展神经元中的生物物理细节和分布的挑战。为其中两个OLM细胞建立了完全加标模型，与它们当前的钳位细胞特异性电生理记录相匹配。总的来说，我们的工作提出了对OLM单元建模的技术进步。我们的模型可供社区使用，以深入了解海马功能潜在的细胞动力学。为其中两个OLM细胞建立了完全加标模型，与它们当前的钳位细胞特异性电生理记录相匹配。总的来说，我们的工作提出了对OLM单元建模的技术进步。我们的模型可供社区使用，以深入了解海马功能潜在的细胞动力学。为其中两个OLM细胞建立了完全加标模型，与它们当前的钳位细胞特异性电生理记录相匹配。总的来说，我们的工作提出了对OLM单元建模的技术进步。我们的模型可供社区使用，以深入了解海马功能潜在的细胞动力学。