NEUROMODULATION AND CORTICAL MEMORY FUNCTION

神经调节和皮质记忆功能

• 批准号: 6692224
• 负责人: Michael E Hasselmo
• 金额: $ 25.44万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-01-06 至 2005-01-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6692224
• 关键词: GABA receptor; Rodentias; acetylcholinesterase; cholinergic receptors; computer simulation; electroencephalography; electrophysiology; entorhinal cortex; evoked potentials; flash photolysis; hippocampus; interneurons; learning; memory; muscarinic receptor; neocortex; neural information processing; neural transmission; neuroregulation; sleep; synapses; wakefulness

DESCRIPTION: (Adapted from the Investigator's Abstract) This continuation application focuses on how different time courses of acetylcholine (ACh) and GABA effects influence the functional dynamics of cortical structures. Preliminary data shows that presynaptic muscarinic and GABAb receptors selectively suppress potentials at excitatory cortical feedback connections, and that these effects have different time courses. ACh and GABA input from the medial septum are associated with theta rhythm oscillation in the hippocampal EEG. Network modeling shows that phasic changes in GABAb modulation of synaptic transmission during theta may enhance sequence storage in hippocampal region CA3. Modeling also shows that suppression of feedback from hippocampus to neocortex by high ACh levels during awake behavior may decrease interference during the encoding of new information in the hippocampus, whereas slow drops in ACh during quite waking and slow wave sleep may set dynamics for consolidation (transfer of information from hippocampus to neocortex). Models motivate testing of two physiological hypotheses: Hypothesis #1. Changes in GABA interneuron activity during theta rhythm oscillations may cause phasic changes in modulation of synaptic potentials. Tests of this hypothesis include measuring size of evoked potentials at different phases of the theta rhythm cycle, testing the time course of GABAb modulation in heterosynaptic depression and after brief applications of GABA, and testing enhancement of encoding by phasic modulation in simulations of hippocampal region CA3. Hypothesis #2. Changes in acetylcholine levels may cause slow state changes in modulation of synaptic feedback from hippocampus to entorhinal cortex. Test of this hypothesis include measuring size of EPSPs induced in entorhinal cortex by stimulation of region CA1 during theta and non-theta EEG states, testing the time course of muscarinic recrptor activation in brain slice preparation, and testing other modulatory effects of acetylcholine in cortical structures. ACh levels and GABAergic interneuron activity change dramatically during different stages of waking and sleep. ACh blockade can cause amnesia and hallucinations. Loss of GABA effects can result in seizures. Disorders of this modulation may contribute to memory deficits in Alzheimers disease and Lewy Body dementia, disorders of REM sleep in depression, and breakdown of slow wave sleep in developmental disorders such as Landau-Kleffner syndrome. Research could guide combined use of drugs influencing GABAb and ACh receptors.

描述：（改编自研究者的摘要） 这个延续应用程序重点关注不同时间课程如何 乙酰胆碱 (ACh) 和 GABA 效应影响功能动态 皮质结构。初步数据表明，突触前毒蕈碱和 GABAb 受体选择性抑制兴奋性皮质反馈电位 联系，并且这些影响有不同的时间进程。乙酰胆碱和伽马氨基丁酸 来自内侧隔膜的输入与 θ 节律振荡相关 海马脑电图。网络模型显示 GABAb 的阶段性变化 θ期间突触传输的调制可以增强序列存储 位于海马区CA3。建模还表明，抑制反馈 清醒行为期间高乙酰胆碱水平可能会导致从海马体到新皮质 减少新信息编码过程中的干扰 海马体，而在完全清醒和慢波睡眠期间乙酰胆碱缓慢下降 可能会设定巩固的动力（信息从海马体转移到 新皮质）。模型激发了对两个生理假设的测试： 假设#1。 θ节律期间 GABA 中间神经元活性的变化 振荡可能会导致突触电位调制的阶段性变化。 该假设的检验包括测量诱发电位的大小 θ节律周期的不同阶段，测试GABAb的时间进程 异质突触抑制的调节以及短暂应用 GABA 后， 并在模拟中测试通过相位调制的编码增强 海马区CA3。 假设#2。乙酰胆碱水平的变化可能会导致缓慢的状态变化 从海马到内嗅皮层的突触反馈的调节。测试 该假设包括测量内嗅皮层中诱导的 EPSP 的大小 在 θ 和非 θ 脑电图状态下刺激 CA1 区，测试 脑切片制备中毒蕈碱受体激活的时间过程，以及 测试乙酰胆碱在皮质结构中的其他调节作用。 ACh 水平和 GABA 能中间神经元活性在 清醒和睡眠的不同阶段。乙酰胆碱阻断可导致健忘症 幻觉。 GABA 作用丧失可能导致癫痫发作。此病症 调节可能导致阿尔茨海默病和路易氏病的记忆缺陷 身体痴呆、抑郁症快速眼动睡眠障碍和慢波崩溃 朗道-克莱夫纳综合征等发育障碍患者的睡眠。研究 可以指导影响 GABAb 和 ACh 受体的药物的联合使用。