Neuromodulation and Cortical Memory Function

描述（由申请人提供）：这个竞争性的延续应用侧重于理解在每个周期的θ节律不同阶段的生理特性变化如何在记忆引导行为所必需的功能动力学中发挥作用。生理实验将测试海马体神经元形成的详细网络模拟的假设，海马体神经元引导虚拟老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，包括来自电流源密度分析的数据，以及显示θ相进动和“分裂细胞”等现象的单元记录数据。我们将测试两个关于记忆引导行为如何被theta节律的特定特征所增强的具体假设：

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.