The wide diversity of inhibitory cells across the brain makes them suitable to contribute to network dynamics in specialized fashions. However, the contributions of a particular inhibitory cell type in a behaving animal are challenging to untangle as one needs to both record cellular activities and identify the cell type being recorded. Thus, using computational modeling and theory to predict and hypothesize cell-specific contributions is desirable. Here, we examine potential contributions of interneuron-specific 3 (I-S3) cells - an inhibitory interneuron found in CA1 hippocampus that only targets other inhibitory interneurons - during simulated theta rhythms. We use previously developed multi-compartment models of oriens lacunosum-moleculare (OLM) cells, the main target of I-S3 cells, and explore how I-S3 cell inputs during in vitro and in vivo scenarios contribute to theta. We find that I-S3 cells suppress OLM cell spiking, rather than engender its spiking via post-inhibitory rebound mechanisms, and contribute to theta frequency spike resonance during simulated in vivo scenarios. To elicit recruitment similar to in vitro experiments, inclusion of disinhibited pyramidal cell inputs is necessary, implying that I-S3 cell firing broadens the window for pyramidal cell disinhibition. Using in vivo virtual networks, we show that I-S3 cells contribute to a sharpening of OLM cell recruitment at theta frequencies. Further, shifting the timing of I-S3 cell spiking due to external modulation shifts the timing of the OLM cell firing and thus disinhibitory windows. We propose a specialized contribution of I-S3 cells to create temporally precise coordination of modulation pathways.

中文翻译：

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破译中间神经元特异性 3 细胞如何控制腔隙分子细胞以促进电路功能

大脑中抑制细胞的广泛多样性使它们适合以专门的方式为网络动态做出贡献。然而，一个特定的抑制细胞类型在行为动物中的贡献是具有挑战性的，因为人们既需要记录细胞活动，又需要识别被记录的细胞类型。因此，使用计算模型和理论来预测和假设细胞特异性贡献是可取的。在这里，我们检查了中间神经元特异性 3 (I-S3) 细胞的潜在贡献 - 在 CA1 海马中发现的一种抑制性中间神经元，仅针对其他抑制性中间神经元 - 在模拟 theta 节律期间。我们使用先前开发的多隔室模型，即 I-S3 细胞的主要靶点，即东方裂隙分子 (OLM) 细胞，并探索在体外和体内情况下 I-S3 细胞输入如何影响 theta。我们发现 I-S3 细胞抑制 OLM 细胞尖峰，而不是通过抑制后反弹机制产生其尖峰，并在模拟的体内场景中促成 theta 频率尖峰共振。为了引起类似于体外实验的募集，必须包含去抑制的锥体细胞输入，这意味着 I-S3 细胞放电拓宽了锥体细胞去抑制的窗口。使用体内虚拟网络，我们表明 I-S3 细胞有助于在 theta 频率下锐化 OLM 细胞募集。此外，由于外部调制而改变 I-S3 细胞尖峰的时间会改变 OLM 细胞放电的时间，从而改变抑制窗口。