The impact of hallucinogens on active sampling and the olfactory bulb

致幻剂对主动采样和嗅球的影响

• 批准号: 10678588
• 负责人: Amanda Colette Welch
• 金额: $ 4.65万
• 依托单位: UNIVERSITY OF OREGON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10678588
• 关键词: Address; Affect; Animal Model; Animals; Area; Behavior; Behavioral; Biological Models; Computer Analysis; Data; Diagnosis; Disease; Environment; Epilepsy; Ethology; Event; Eye Movements; Goals; Hallucinations; Hallucinogens; Head; Head Movements; Human; Implant; Machine Learning; Measures; Mediating; Mental disorders; Methods; Migraine; Molecular; Movement; Mus; Neurons; Odors; Olfactory Cortex; Olfactory Hallucinations; Olfactory Pathways; Parkinson Disease; Perception; Perceptual disturbance; Pharmaceutical Preparations; Policies; Psilocybin; Reporting; Research; Resolution; Saline; Sampling; Schizophrenia; Sensory; Serotonergic System; Smell Perception; Source; Stimulus; Structure; System; Testing; Training; Visual Hallucination; Work; experience; insight; multi-electrode arrays; nervous system disorder; neural; neural circuit; neuromechanism; neurophysiology; olfactory bulb; receptor; receptor expression; response; tool; verbal

PROJECT SUMMARY Olfactory hallucinations occur in many disorders, including Parkinson’s disease, epilepsy, schizophrenia, and migraines, but the neural mechanisms underlying these hallucinations are unknown. Mice have a powerful olfactory system that is well-studied at the molecular, systems, and behavioral levels. Importantly, hallucinogens such as LSD, psilocybin, and DOI primarily act on serotonin pathways, which feed heavily into the mouse olfactory system. The proposed research will determine the behavioral changes in olfactory-driven behaviors and identify the impact on neural activity in the olfactory bulb. Mechanistic studies of hallucination in animal models are fundamentally limited, since other animals do not verbalize what they perceive. However, in lieu of a verbal report, internal states can be inferred from an animal’s externally observable behavior. Using machine-learning tools, our lab has shown that a mouse’s behavioral states can be inferred from close analysis of sniffing and movement. In this project, we will investigate the mouse hallucinogen response using high resolution behavioral analysis and neuronal ensemble recordings in the olfactory bulb. We hypothesize that hallucinogens will impact olfactory perceptual reports and strategic sniffing behavior. Further, we hypothesize that the neural activity in the olfactory bulb will resemble odor-evoked activity in the absence of odor after hallucinogen administration. To address our hypothesis about perceptual reports, in aim 1 we will train freely-moving mice on a two- alternative choice task to locate the source of an odor while recording movement and sniffing. After the mice are trained, we will administer DOI or saline. Our hypothesis predicts that DOI will induce false alarms, decrease accuracy, and decrease confidence in the presence of an odor stimulus. To address our hypothesis about neural activity, in aim 2 we will record movement, sniffing, and neural activity in the olfactory bulb during spontaneous, uninstructed, freely-moving behavior. We will test the prediction that hallucinogen administration alters the neural dynamics of the olfactory bulb to resemble odor-evoked activity in the absence of an odor stimulus. Completion of this proposal will provide insight into the behavior and neural circuitry of olfaction and help inform treatment and policy on the use of hallucinogens to treat various disorders.

项目摘要 嗅觉幻觉发生在许多疾病中，包括帕金森氏病，癫痫，精神分裂症和 偏头痛，但是这些幻觉的神经机制尚不清楚。老鼠有强大的 在分子，系统和行为水平上进行了充分研究的嗅觉系统。重要的是， 诸如LSD，psilocybin和DOI诸如5-羟色胺途径的主要作用，它们大量进食 鼠标嗅觉系统。拟议的研究将确定嗅觉驱动的行为变化 行为并确定对嗅球中神经活动的影响。 动物模型中幻觉的机理研究从根本上有限，因为其他动物不 口头表达他们的感知。但是，代替了口头报告，可以从 动物的外部可观察的行为。使用机器学习工具，我们的实验室表明鼠标的 行为状态可以通过对嗅探和运动的密切分析来推断。在这个项目中，我们将 使用高分辨率行为分析和神经元合奏研究小鼠致幻剂反应 嗅球中的录音。我们假设致幻剂会影响嗅觉感知 报告和战略嗅探行为。此外，我们假设嗅觉中的神经活动 在致幻剂给药后没有气味的情况下，灯泡将类似于气味诱发的活性。 为了解决我们关于感知报告的假设，在AIM 1中，我们将在两种情况下训练自由移动的小鼠 录制运动和嗅探时，可以找到气味的替代选择任务。在老鼠之后 经过训练，我们将管理DOI或盐水。我们的假设预测DOI将引起虚假警报， 在存在气味刺激的情况下，降低准确性并降低置信度。解决我们的假设 关于神经活动，在AIM 2中，我们将记录嗅球中的运动，嗅探和神经活动 赞助，独立，自由移动的行为。我们将测试幻觉剂给药的预测 在没有气味的情况下改变嗅球的神经动力学，类似于气味诱发的活性 刺激。该提案的完成将洞悉嗅觉的行为和神经回路 帮助告知治疗和政策有关使用致幻剂治疗各种疾病的治疗和政策。