Neurophysiological impacts of hallucinogens on hippocampal and cortical neural circuits

致幻剂对海马和皮质神经回路的神经生理学影响

• 批准号: 10591612
• 负责人: Daoyun Ji
• 金额: $ 36万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10591612
• 关键词: Animals; Anxiety Disorders; Area; Behavior; Behavioral; Brain; Cells; Cognition; Cues; Data; Detection; Drug abuse; Event; Hallucinations; Hallucinogens; Head; Hippocampus; Human; Immobilization; Impairment; Investigational Therapies; Knowledge; Learning; Location; Lysergic Acid Diethylamide; Memory; Memory impairment; Mental Depression; Mental disorders; Neurons; Neurophysiology - biologic function; Outcome; Outcome Study; Pattern; Perception; Performance; Pharmaceutical Preparations; Prefrontal Cortex; Property; Rattus; Research; Risk; Rodent; Role; Running; Schizophrenia; Sensory; Short-Term Memory; Sleep; Sleep Architecture; Slow-Wave Sleep; Symptoms; Task Performances; Techniques; Testing; Therapeutic; Time; Training; Visual; Visual Cortex; awake; behavioral response; cognitive function; dosage; drug addiction therapy; human imaging; imaging study; in vivo; insight; interest; memory consolidation; memory process; memory retrieval; neural; neural circuit; neurophysiology; novel; novel therapeutics; psychotic; receptor; response; sensory cortex; spatial memory; treatment strategy; voltage; way finding

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.

项目总结 近年来，人们对使用迷幻剂作为实验性治疗方法的兴趣急剧增加。 吸毒、抑郁和焦虑症。然而，迷幻剂也是改变神经的强效药物。 大脑的功能。要了解它们的潜在好处或风险，重要的是确定 迷幻剂对活体神经回路的神经生理学影响。迷幻药麦角酸 二乙胺(LSD)是一种经典的迷幻剂，可以改变人类的感知和认知功能 动物。本项目研究LSD对感觉和记忆神经回路的神经生理学影响。 无拘无束的老鼠。我们将专注于一个假设，即视觉皮质和大脑 LSD减少了海马区，导致了活跃空间中不精确的空间表征 在离线行为中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区的神经元 在LSD状态下的大鼠学习或执行空间工作记忆任务时，以及在睡眠时的视觉皮质。 我们将确定LSD如何改变海马区和视皮层的活动及其相互作用 活动和静止行为以及在睡眠中，这些变化如何依赖于LSD剂量和5-羟色胺能 5HT2A受体，它们如何与行为任务表现相关，以及如何增强它们 或者通过操纵典型的活动和离线行为的网络振荡来缓解。这项研究将揭示 迷幻药物LSD的体内神经生理效应，促进了我们对如何 感觉和记忆回路的改变可能有助于药物和药物引起的精神状态 精神障碍，如精神分裂症，并发现潜在的风险时，迷幻剂被探索为 治疗药物成瘾和精神障碍的新疗法。