Dur-e-Ahmad Muhammad, Nicola Wilten, Campbell Sue Ann, Skinner Frances K
Department of Applied Mathematics, University of Waterloo, Waterloo, ON, Canada.
J Comput Neurosci. 2012 Aug;33(1):21-40. doi: 10.1007/s10827-011-0372-6. Epub 2011 Dec 2.
The hippocampus is a brain structure critical for memory functioning. Its network dynamics include several patterns such as sharp waves that are generated in the CA3 region. To understand how population outputs are generated, models need to consider aspects of network size, cellular and synaptic characteristics and context, which are necessarily 'balanced' in appropriate ways to produce particular outputs. Thick slice hippocampal preparations spontaneously produce sharp waves that are initiated in CA3 regions and depend on the right balance of glutamatergic activities. As a step toward developing network models that can explain important balances in the generation of hippocampal output, we develop models of CA3 pyramidal cells. Our models are single compartment in nature, use an Izhikevich-type structure and involve parameter values that are specifically designed to encompass CA3 intrinsic properties. Importantly, they incorporate spike frequency adaptation characteristics that are directly comparable to those measured experimentally. Excitatory networks using these model cells are able to produce bursting suggesting that the amount of spike frequency adaptation expressed in the biological cells is an essential contributor to network bursting, and as such, may be important for sharp wave generation. The network bursting mechanism is numerically dissected showing the critical balance between adaptation and excitatory drive. The compact nature of our models allows large network simulations to be efficiently computed. This, together with the linkage of our models to cellular characteristics, will allow us to develop an understanding of population output of CA3 hippocampus with direct biological comparisons.
海马体是对记忆功能至关重要的脑结构。其网络动态包括多种模式,如在CA3区域产生的尖波。为了理解群体输出是如何产生的,模型需要考虑网络大小、细胞和突触特征以及环境等方面,这些方面必须以适当的方式“平衡”,以产生特定的输出。厚切片海马体制备物会自发产生起源于CA3区域并依赖于谷氨酸能活动适当平衡的尖波。作为朝着开发能够解释海马体输出产生中重要平衡的网络模型迈出的一步,我们开发了CA3锥体细胞模型。我们的模型本质上是单室的,采用Izhikevich型结构,并涉及专门设计以涵盖CA3内在特性的参数值。重要的是,它们纳入了与实验测量值直接可比的放电频率适应特性。使用这些模型细胞的兴奋性网络能够产生爆发,这表明生物细胞中表达的放电频率适应量是网络爆发的重要促成因素,因此可能对尖波产生很重要。对网络爆发机制进行了数值剖析,显示了适应与兴奋性驱动之间的关键平衡。我们模型的紧凑性质允许高效地计算大型网络模拟。这一点,再加上我们的模型与细胞特征的联系,将使我们能够通过直接的生物学比较来理解CA3海马体的群体输出。