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：（根据调查员的摘要进行了改编） 这种延续申请的重点是不同的时间课程 乙酰胆碱（ACH）和GABA效应影响的功能动力学 皮质结构。初步数据表明，突触前毒蕈碱和 GABAB受体在兴奋性皮质反馈下有选择地抑制电势 连接，这些效果具有不同的时间课程。 ACH和GABA 内侧隔膜的输入与theta节律振荡有关 海马脑电图。网络建模表明GABAB的阶段变化 theta期间突触传播的调节可能会增强序列存储 在海马区CA3中。建模还表明反馈的抑制 在清醒行为期间，从海马到新皮层，可能 减少在编码新信息期间的干扰 海马，而醒来时ACH的慢下降和慢速睡眠 可以设置合并的动力学（将信息从海马转移到 NeoCortex）。模型促使测试两个生理假设： 假设1。 theta节奏期间GABA中间神经元活动的变化 振荡可能导致突触电位调节的阶段变化。 该假设的测试包括测量诱发电位的大小 theta节律周期的不同阶段，测试GABAB的时间过程 杂突抑郁症的调节以及在GABA短暂应用之后 以及通过阶段调制对编码增强的模拟 海马区CA3。 假设2。乙酰胆碱水平的变化可能会导致状态缓慢变化 从海马到内嗅皮层的突触反馈调节。测试 该假设包括测量通过 刺激theta和非theta脑电图期间的区域CA1，测试 毒蕈碱招募者在脑切片制备中激活的时间过程， 测试乙酰胆碱在皮质结构中的其他调节作用。 在期间 醒来和睡眠的不同阶段。 ACH封锁会导致失忆和 幻觉。 GABA效应的丧失会导致癫痫发作。这种疾病 调节可能导致阿尔茨海默氏病和路易的记忆缺陷 身体痴呆，抑郁症中REM睡眠障碍以及慢波崩溃 在发育障碍中睡眠，例如Landau-Kleffner综合征。研究 可以指导影响GABAB和ACH受体的药物的联合使用。