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Use of compartmental models to predict physiological properties of hippocampal inhibitory neurons.

机译：使用隔室模型预测海马抑制神经元的生理特性。

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摘要

Inhibitory neurons, or interneurons, which make up only 10-15% of the neuronal population in the hippocampus are thought to control and sculpt field rhythms through their contact with hundreds of excitatory cells, or pyramidal neurons. Interneurons are heterogeneous in terms of their morphologies, biophysical properties, and their presynaptic or postsynaptic targets. These heterogeneities are thought to have functional significance. We hypothesize that biophysical parameters of neurons can be determined by a variety of simulations using morphologically realistic multi-compartment neuron models. Virtual experiments, which would be difficult or impossible to perform in real experiments, can be used to place constraints on such parameters as the ion channel content of distal dendrites or the location of electrical synapses between neurons.; The aim of this dissertation was to use compartmental models to predict physiological parameters of hippocampal inhibitory neurons. The oriens-lacunosum/moleculare (O-LM) and basket cell interneurons were the focus of this work due to the availability of biophysical data for these interneuron subtypes.; Kinetic model parameters were determined for the muscarinic potassium current, IM, by using multi-compartment models of O-LM interneurons with various IM somato-dendritic distributions. The simulations predicted conductance densities for each distribution to match experiments. Using a reverse engineering approach, the steady-state activation curves of IM were predicted in simulations to match whole cell recordings from experiments. Using sinusoidal current inputs, the O-LM interneuron models displayed a resonance at theta frequencies which could be expanded with block of IM, particularly for suprathreshold sinusoidal inputs.; The basket cell models were used in two-cell networks to explore how location and strength of electrical coupling affects network spiking patterns. Proximal gap junctions resulted in pure synchrony patterns for all gap junctional strengths and all intrinsic frequencies explored. Middle and distal dendritic gap junctional locations produced a variety of network patterns including pure synchrony, phase-locked and anti-phase.; Both interneuron types have been shown experimentally to contribute to the theta/gamma field rhythms that have been measured in vivo during exploration and learning. Speculations on the possible role of the parameters explored here are discussed within the context of the theta/gamma field rhythms and the hippocampal circuitry.
机译：抑制性神经元或中间神经元仅占海马神经元总数的10-15％，据认为是通过与数百个兴奋性细胞或锥体神经元接触来控制和塑形场节律的。中间神经元在其形态，生物物理特性以及它们的突触前或突触后靶标方面是异质的。这些异质性被认为具有功能意义。我们假设神经元的生物物理参数可以通过使用形态学逼真的多室神经元模型的各种模拟来确定。虚拟实验，在实际实验中很难或不可能执行，可以用来对诸如远端树突的离子通道含量或神经元之间的电突触的位置等参数施加约束。本文的目的是利用隔室模型预测海马抑制神经元的生理参数。由于这些中间神经元亚型的生物物理数据的可用性，原始的/腔/分子（O-LM）和篮状细胞中间神经元是这项工作的重点。通过使用具有各种IM体树突状分布的O-LM中间神经元多室模型，确定毒蕈碱钾电流IM的动力学模型参数。模拟预测了每种分布的电导密度，以匹配实验。使用逆向工程方法，可以在模拟中预测IM的稳态激活曲线，以匹配实验中的整个细胞记录。使用正弦电流输入，O-LM中间神经元模型在theta频率处显示出谐振，该谐振可以通过IM块扩展，特别是对于超阈值正弦输入。篮式单元模型用于两单元网络中，以探索电耦合的位置和强度如何影响网络峰值模式。近端间隙连接导致所有间隙连接强度和所有固有频率的纯同步模式。树突间隙的中部和远端连接位置产生了多种网络模式，包括纯同步，锁相和反相。两种中间神经元类型均已通过实验证明对在探索和学习过程中体内测得的theta /γ场节律有贡献。在θ/γ场节律和海马回路的背景下讨论了对此处探讨的参数可能作用的推测。

著录项

  • 作者

    Saraga, Fernanda.;

  • 作者单位

    University of Toronto (Canada).;

  • 授予单位 University of Toronto (Canada).;
  • 学科 Biology Neuroscience.
  • 学位 Ph.D.
  • 年度 2006
  • 页码 205 p.
  • 总页数 205
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经科学;
  • 关键词

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