Siekmeier Peter J
Harvard Medical School and McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA.
Behav Brain Res. 2009 Jun 8;200(1):220-31. doi: 10.1016/j.bbr.2009.01.021.
The manner in which hippocampus processes neural signals is thought to be central to the memory encoding process. A theoretically oriented literature has suggested that this is carried out via "attractors" or distinctive spatio-temporal patterns of activity. However, these ideas have not been thoroughly investigated using computational models featuring both realistic single-cell physiology and detailed cell-to-cell connectivity. Here we present a 452 cell simulation based on Traub et al.'s pyramidal cell [Traub RD, Jefferys JG, Miles R, Whittington MA, Toth K. A branching dendritic model of a rodent CA3 pyramidal neurone. J Physiol (Lond) 1994;481:79-95] and interneuron [Traub RD, Miles R, Pyramidal cell-to-inhibitory cell spike transduction explicable by active dendritic conductances in inhibitory cell. J Comput Neurosci 1995;2:291-8] models, incorporating patterns of synaptic connectivity based on an extensive review of the neuroanatomic literature. When stimulated with a one second physiologically realistic input, our simulated tissue shows the ability to hold activity on-line for several seconds; furthermore, its spiking activity, as measured by frequency and interspike interval (ISI) distributions, resembles that of in vivo hippocampus. An interesting emergent property of the system is its tendency to transition from stable state to stable state, a behavior consistent with recent experimental findings [Sasaki T, Matsuki N, Ikegaya Y. Metastability of active CA3 networks. J Neurosci 2007;27:517-28]. Inspection of spike trains and simulated blockade of K(AHP) channels suggest that this is mediated by spike frequency adaptation. This finding, in conjunction with studies showing that apamin, a K(AHP) channel blocker, enhances the memory consolidation process in laboratory animals, suggests the formation of stable attractor states is central to the process by which memories are encoded. Ways that this methodology could shed light on the etiology of mental illness, such as schizophrenia, are discussed.
海马体处理神经信号的方式被认为是记忆编码过程的核心。一篇理论导向的文献表明，这是通过“吸引子”或独特的时空活动模式来实现的。然而，这些观点尚未通过具有现实单细胞生理学和详细细胞间连接性的计算模型进行彻底研究。在此，我们基于特劳布等人的锥体细胞[特劳布RD，杰弗里斯JG，迈尔斯R，惠廷顿MA，托特K。啮齿动物CA3锥体细胞的分支树突模型。《生理学杂志》（伦敦）1994年；481：79 - 95]和中间神经元[特劳布RD，迈尔斯R，锥体细胞到抑制性细胞的尖峰转导可由抑制性细胞中的活性树突电导解释。《计算神经科学杂志》1995年；2：291 - 298]模型进行了452个细胞的模拟，该模型基于对神经解剖学文献的广泛综述纳入了突触连接模式。当用一秒钟的生理现实输入进行刺激时，我们模拟的组织显示出在线保持活动数秒的能力；此外，其尖峰活动，通过频率和峰间间隔（ISI）分布来衡量，类似于体内海马体的尖峰活动。该系统一个有趣的涌现特性是它倾向于从一个稳定状态转变到另一个稳定状态，这种行为与最近的实验结果一致[佐佐木T，松木N，池谷Y。活跃的CA3网络的亚稳定性。《神经科学杂志》2007年；27：517 - 528]。对尖峰序列的检查以及对K（AHP）通道的模拟阻断表明，这是由尖峰频率适应介导的。这一发现，结合表明阿帕明（一种K（AHP）通道阻滞剂）可增强实验动物记忆巩固过程的研究，表明稳定吸引子状态的形成是记忆编码过程的核心。本文还讨论了这种方法可能为精神疾病（如精神分裂症）的病因学提供线索的方式。
