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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.

项目总结