Models of behavior and spike timing in sequence memory

将使用海马体结构、内嗅觉皮质和前额叶皮质的计算模型 在老鼠和人类的行为任务中模拟记忆引导的行为。这些模拟将扩展 本实验室以前的建模工作(Hasselmo等人，2002b；Fransen等人，2002；Koene等人，2003； Hasselmo，2005a；Koene和Hasselmo，2005；Hasselmo和Eichenbaum，2005)来生成预测 关于一系列不同记忆引导任务中的生理数据。中的行为操作选择 模型依赖于输入刺激序列的编码和上下文相关检索(即 剧集)。这些模型将为该中心的特定研究项目生成预测，包括： 1)神经元放电时间与刺激和海马theta相关预测的产生 大鼠在有气味的顺序再认任务中的节律 与订单识别的正确与不正确性能相关的fMRI激活的大小 人类的任务， 2.)脑内神经元放电的上下文相关特性和theta相预测的产生 气味序列歧义消除任务和fMRI激活的大小 与人类在消解歧义任务中的选择有关， 3.)生成关于T-迷宫中延迟的不匹配放置(DNMP)任务的预测，涉及分离器细胞反应和序列读出相对于theta节律和 行为与不同时相刺激引起的行为反应 不同的任务周期。 这些模拟将使用神经元网络，从阈值单元开始，并使用详细的 隔室生物物理模拟，将网络动力学与本征电流和子类 海马区和内嗅区皮质内的神经元。从这项工作中获得的见解将改善我们的 了解海马体和相关皮质的正常功能，可能有助于 治疗阿尔茨海默病或精神分裂症等障碍中的记忆障碍。

Computational models of the hippocampal formation, entorhinal cortex and prefrontal cortex will be used to simulate memory-guided behavior in both rat and human behavioral tasks. These simulations will extend previous modeling work in this laboratory (Hasselmo et al., 2002b; Fransen et al., 2002; Koene et al., 2003; Hasselmo, 2005a; Koene and Hasselmo, 2005; Hasselmo and Eichenbaum, 2005) to generate predictions about physiological data in a range of different memory-guided tasks. Selection of behavioral actions in the model depends on the encoding and context dependent retrieval of sequences of input stimuli (i.e. episodes). The models will generate predictions for specific research projects in the center, including: 1.) generation of predictions about the timing of neuron firing relative to stimuli and hippocampal theta rhythm during performance of the order recognition task with odors in rats, and the magnitude of fMRI activation associated with correct versus incorrect performance of an order recognition task in humans, 2.) generation of predictions about context-dependent properties and theta phase of neuronal firing in the odor sequence disambiguation task, and the magnitude of fMRI activation associated with choice in a disambiguation task in humans, 3.) generation of predictions about the delayed non-match to place (DNMP) task in the T-maze, concerning the timing of splitter cell responses and sequence readout relative to theta rhythm and behavior and the disruption of behavioral responses caused by stimulation at different phases of theta during different task periods. These simulations will use networks of neurons starting with threshold units and building to use of detailed compartmental biophysical simulations, to relate network dynamics to intrinsic currents and subclasses of neurons within the hippocampus and entorhinal cortex. The insights gained from this work will improve our understanding of the normal function of the hippocampus and associated cortex, potentially contributing to treatment of memory impairments in disorders such as Alzheimer's disease or schizophrenia.