NEUROMODULATION AND CORTICAL MEMORY FUNCTION

描述：（改编自研究者摘要） 这个延续应用程序的重点是如何不同的时间过程中， 乙酰胆碱（ACh）和GABA的影响的功能动力学 皮质结构初步数据显示，突触前毒蕈碱和 GABAb受体选择性抑制兴奋性皮层反馈电位 连接，并且这些影响具有不同的时间过程。ACh和GABA 来自内侧隔的输入与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 在theta期间突触传递的调制可以增强序列存储 海马CA 3区。模型还表明，抑制反馈 从海马到新皮层的高ACh水平在清醒的行为， 减少在新信息的编码期间的干扰 海马体，而在完全清醒和慢波睡眠期间ACh缓慢下降 可以设置用于巩固的动力学（将信息从海马体传递到 neocortex）。模型激发了两个生理假设的测试： 假设#1。θ节律时GABA中间神经元活性的变化 振荡可引起突触电位调制的相位变化。 这一假设的测试包括测量诱发电位的大小， θ节律周期的不同阶段，测试GABAb的时程 在异突触抑制中的调制和在短暂应用GABA后， 以及测试在模拟中通过相位调制的编码增强， 海马CA 3区。 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制。试验 这一假设包括测量内嗅皮层中诱发的EPSP的大小， 在θ和非θ EEG状态期间刺激区域CA 1，测试 脑切片制备中毒蕈碱受体激活的时间过程，和 测试乙酰胆碱在皮质结构中的其他调节作用。 期间ACh水平和GABA能中间神经元活动发生显着变化 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效应的丧失可能导致癫痫发作。这种疾病 调制可能导致阿尔茨海默病和路易 躯体痴呆、抑郁症的快速眼动睡眠障碍和慢波崩溃 睡眠在发育障碍中的作用，如Landau-Kleffner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.