Neuromodulation and Cortical Memory Function

描述（由申请人提供）：该竞争性继续申请侧重于了解θ节律每个周期不同阶段的生理特性变化如何在记忆引导行为所需的功能动力学中发挥作用。生理学实验将测试海马结构神经元的详细网络模拟的假设，海马结构指导虚拟大鼠在虚拟环境中执行记忆引导的行为任务。这些模型复制了清醒行为动物的电生理记录，包括电流源密度分析的数据，以及显示θ相位进动和“分裂细胞”等现象的单位记录数据。我们将测试两个关于记忆引导行为如何被θ节律的特定特征增强的特定假设： 假设#1。θ节律期间LTP和突触输入的变化提供了海马回路中编码和提取的独立阶段。 假设2。突触输入的时相定时为记忆引导行为提供了最有效的情景提取。 这些假设的检验包括测量暴露于新环境期间相对于θ节律的单位的时间，测量执行延迟匹配样本任务期间前额叶皮层和海马中相对于θ节律的θ相位重置和尖峰时间，测试不同路径长度的延迟空间交替期间相对于θ节律的单位活动，在线性轨道中测试随机探索和单侧奖励期间的单位活动，测试由投射到腔隙分子层的定向层中的中间神经元的激活介导的突触传递的调节的时间过程。I-m），并测试mGluR调制传输的时间过程，单位为s。我...了解这些机制可能有助于开发阿尔茨海默病的药物治疗。

DESCRIPTION (provided by applicant): This competing continuation application focuses on understanding how changes in physiological properties at different phases of each cycle of the theta rhythm play a role in the functional dynamics necessary for memory guided behavior. Physiological experiments will test hypotheses from detailed network simulations of neurons in the hippocampal formation, which guide the movements of a virtual rat in a virtual environment performing memory-guided behavioral tasks. These models replicate electrophysiological recordings from awake behaving animals, including data from current source density analysis, and unit recording data showing phenomena such as theta phase precession and "splitter cells". We will test two specific hypotheses about how memory-guided behavior is enhanced by specific features of theta rhythm: Hypothesis #1. Changes in LTP and synaptic input during theta rhythm provide separate phases of encoding and retrieval in hippocampal circuits. Hypothesis #2. Phasic timing of synaptic input provides the most effective episodic retrieval for memory-guided behavior. Tests of these hypotheses include measuring timing of units relative to theta rhythm during exposure to a novel environment, measuring theta phase reset and spike timing relative to theta rhythm in prefrontal cortex and hippocampus during performance of a delayed match to sample task, testing unit activity relative to theta rhythm during delayed spatial alternation with different path lengths, testing unit activity during random exploration and single sided reward in a linear track, testing time course of modulation of synaptic transmission mediated by activation of interneurons in stratum oriens projecting to stratum lacunosummolecutare (s. I-m), and testing time course of mGluR modulation of transmission in s. I-m. Understanding these mechanisms may assist in development of pharmacological treatments for Alzheimer's disease.