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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要近年来，人们对使用迷幻药作为实验疗法的兴趣急剧增加药物成瘾、抑郁症和焦虑症。然而，致幻剂也是改变神经的强效药物。大脑中的功能。要了解其潜在的好处或风险，重要的是确定迷幻药对体内神经回路的神经生理学影响。迷幻药麦角酸二乙酰胺（LSD）是一种经典的致幻剂，可以改变人类的知觉和认知功能动物。该项目研究 LSD 对感觉和记忆神经回路的神经生理学影响在自由行为的老鼠中。我们将重点关注视觉皮层和视觉皮层之间的相互作用的假设 LSD 会导致海马体减少，从而导致活动空间期间的空间表征不精确离线行为期间的导航和受损的神经活动重新激活对记忆很重要检索和整合。为了检验这个假设，我们将同时记录海马体中的神经元当老鼠在 LSD 下学习或执行空间工作记忆任务以及睡觉时，视觉皮层。我们将确定 LSD 期间如何改变海马和视觉皮层活动及其相互作用。活跃和不动的行为以及睡眠期间，这些变化如何取决于 LSD 剂量和血清素能 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活跃和离线行为典型的网络振荡来缓解。这项研究将揭示迷幻药物 LSD 的体内神经生理学效应，加深了我们对如何感觉和记忆回路的改变可能会导致药物和药物产生的精神病状态精神疾病，如精神分裂症，并在探索迷幻药时发现潜在风险药物成瘾和精神障碍的新疗法。