Krembil Brain Institute, University Health Network, Toronto, Canada.
Department of Physiology, University of Toronto, Toronto, Canada.
Hippocampus. 2021 Sep;31(9):982-1002. doi: 10.1002/hipo.23364. Epub 2021 Jun 4.
The wide variety of cell types and their biophysical complexities pose a challenge in our ability to understand oscillatory activities produced by cellular-based computational network models. This challenge stems from their high-dimensional and multiparametric natures. To overcome this, we implement a solution by linking minimal and detailed models of CA1 microcircuits that generate intrahippocampal (3-12 Hz) theta rhythms. We leverage insights from minimal models to guide explorations of more detailed models and obtain a cellular perspective of theta generation. Our findings distinguish the pyramidal cells as the theta rhythm initiators and reveal that their activity is regularized by the inhibitory cell populations, supporting a proposed hypothesis of an "inhibition-based tuning" mechanism. We find a strong correlation between input current to the pyramidal cells and the resulting local field potential theta frequency, indicating that intrinsic pyramidal cell properties underpin network frequency characteristics. This work provides a cellular-based foundation from which in vivo theta activities can be explored.
细胞类型的多样性及其生物物理复杂性给我们理解基于细胞的计算网络模型产生的振荡活动的能力带来了挑战。这一挑战源于其高维性和多参数性质。为了克服这一挑战,我们通过链接生成海马内(3-12 Hz)θ节律的 CA1 微电路的最小和详细模型来实施解决方案。我们利用最小模型的见解来指导对更详细模型的探索,并获得对θ生成的细胞视角。我们的发现将锥体细胞区分出来作为θ节律的启动子,并揭示它们的活动受到抑制细胞群体的调节,支持了一种“基于抑制的调谐”机制的假设。我们发现,向锥体细胞输入的电流与产生的局部场电位θ频率之间存在很强的相关性,这表明内在的锥体细胞特性是网络频率特征的基础。这项工作为探索体内θ活动提供了一个基于细胞的基础。