NEUROMODULATION AND CORTICAL MEMORY FUNCTION

描述：(改编自《调查者摘要》) 此延续应用程序侧重于不同的时间进程如何 乙酰胆碱(ACh)和GABA效应影响中枢神经系统功能动力学 皮质结构。初步数据显示，突触前毒鼠强和 GABAB受体选择性抑制兴奋性皮层反馈电位 这些影响具有不同的时间进程。ACh和GABA 内侧隔区的输入与内侧隔区的theta节律振荡有关 海马区的脑电波。网络模拟表明，GABAB的阶段性变化 在theta期间对突触传输的调制可以增强序列存储 在海马区CA3。建模还表明，反馈的抑制 在清醒行为中，高水平的ACh可能会导致从海马区到大脑皮层 减少在编码新信息期间的干扰 海马区，而在完全清醒和慢波睡眠期间ACh缓慢下降 可以设置巩固的动力(将信息从海马体传输到 新大脑皮层)。模型激发了对两个生理假设的测试： 假设1.Theta节律期间GABA中间神经元活性的变化 振荡可引起突触电位调制的阶段性变化。 对这一假设的检验包括测量诱发电位的大小 Theta节律周期的不同阶段，测试GABAB的时间进程 异突触抑制中的调制以及GABA的简单应用后， 并在仿真中测试了相位调制对编码的增强 海马区CA3。 假设2.乙酰胆碱水平的变化可能会导致大脑中缓慢的状态变化 从海马体到内嗅皮层的突触反馈的调制。测试 这一假设包括测量在内嗅皮质中诱导的EPSP的大小 在theta和非theta脑电状态下刺激CA1区，测试 脑片制备过程中M受体激活的时程 测试乙酰胆碱在大脑皮层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。每一次封锁都会导致失忆和 幻觉。GABA效应的丧失会导致癫痫发作。这是一种疾病 阿尔茨海默病和路易斯病患者的记忆障碍可能与调制有关 躯体痴呆、抑郁症的快速眼动睡眠障碍和慢波崩溃 睡眠中的发育障碍，如兰道-克莱夫纳综合征。研究 可指导联合应用影响GABAB和ACh受体的药物。

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.