Neurophysiological impacts of hallucinogens on hippocampal and cortical neural circuits

项目摘要 近年来，人们对使用致幻剂作为实验性治疗方法的兴趣急剧增加， 药物成瘾抑郁和焦虑症然而，致幻剂也是一种强效药物， 在大脑中的功能。为了了解其潜在的益处或风险，重要的是要确定 致幻药对体内神经回路的神经生理学影响。迷幻药麦角酸 二乙基酰胺（LSD）是一种经典的致幻剂，可以改变人类的感知和认知功能， 动物该项目研究LSD对感觉和记忆神经回路的神经生理影响 在自由行为的老鼠身上。我们将集中讨论一个假设，即视觉皮层和大脑皮层之间的相互作用， 海马被LSD减少，这导致在主动空间表达期间不精确的空间表达。 在离线行为期间，导航和受损的神经活动重新激活对记忆很重要 检索和合并。为了验证这一假设，我们将同时记录海马体中的神经元 和视觉皮层，而LSD大鼠学习或执行空间工作记忆任务，而他们睡觉。 我们将确定LSD如何改变海马和视觉皮层的活动及其相互作用， 活动和不动的行为和在睡眠中，如何改变取决于LSD剂量和多巴胺能神经递质 5HT2A受体，它们如何与行为任务表现相关，以及它们如何被增强 或者通过操纵典型的活动和离线行为的网络振荡来减轻。这项研究将揭示 迷幻药LSD的体内神经生理学效应，推进了我们对 感觉和记忆回路的改变可能导致药物引起的精神病状态， 精神疾病，如精神分裂症，并发现潜在的风险时，迷幻剂被探索， 药物成瘾和精神障碍的新疗法。

PROJECT SUMMARY Recent years have seen a dramatic increase in the interest of using psychedelics as experimental therapies for drug addition, depression and anxiety disorders. However, psychedelics are also powerful drugs that alter neural functions in the brain. To understand their potential benefits or risks, it is important to determine the neurophysiological effects of psychedelics on neural circuits in vivo. The psychedelic drug lysergic acid diethylamide (LSD) is a classic hallucinogen that can alter perceptual and cognitive functions in humans and animals. This project studies the neurophysiological impacts of LSD on the sensory and memory neural circuits in freely behaving rats. We will focus on a hypothesis that the interactions between the visual cortex and the hippocampus are reduced by LSD, which leads to imprecise spatial representations during active spatial navigation and impaired neural activity reactivations during offline behavior that are important for memory retrieval and consolidation. To test the hypothesis, we will simultaneously record neurons in the hippocampus and the visual cortex while rats under LSD learn or perform a spatial working memory task and while they sleep. We will determine how hippocampal and visual cortical activities and their interactions are altered by LSD during active and immobile behavior and during sleep, how the alterations depend on LSD dosage and the serotonergic 5HT2A receptors, how they are correlated with behavioral task performances, and how they can be augmented or alleviated by manipulating the network oscillations typical of active and offline behavior. This study will reveal the in vivo neurophysiological effects of the psychedelic drug LSD, advance our understanding on how alterations in the sensory and memory circuits may contribute to the psychotic state generated by drugs and in psychiatric disorders such as schizophrenia, and uncover potential risks when psychedelics are explored as novel therapies for drug addiction and mental disorders.