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， 偏头痛，但这些幻觉背后的神经机制尚不清楚。老鼠有强大的 嗅觉系统是在分子、系统和行为水平上得到充分研究的系统。重要的是， 致幻剂如LSD、裸盖菇素和DOI主要作用于血清素途径，这些途径大量进入 老鼠的嗅觉系统这项研究将确定嗅觉驱动的行为变化 行为，并确定对嗅球神经活动的影响。 在动物模型中对幻觉机制的研究基本上是有限的，因为其他动物没有 说出他们所感知的。然而，代替口头报告，内部状态可以从 动物的外在行为。使用机器学习工具，我们的实验室已经证明， 行为状态可以从对嗅闻和运动的密切分析中推断出来。在这个项目中，我们将 用高分辨率行为分析和神经元集成研究小鼠致幻剂反应 记录在嗅球里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，在嗅觉神经活动 在给予致幻剂后，在没有气味的情况下，灯泡将类似于气味诱发的活动。 为了解决我们关于感知报告的假设，在目标1中，我们将在两个- 另一项选择任务是在记录运动和嗅闻的同时找到气味的来源。小鼠后 接受过培训的人，我们将给予DOI或生理盐水。我们的假设预测DOI会引起假警报， 降低准确性，并降低对气味刺激存在的信心。为了证实我们的假设 关于神经活动，在目标2中，我们将记录运动，嗅探和嗅球中的神经活动， 自发的，未经指导的，自由移动的行为我们将检验迷幻剂的使用 改变嗅球的神经动力学，使其类似于没有气味时的气味诱发活动 刺激。完成这一建议将提供深入了解的行为和神经回路的嗅觉， 帮助为使用致幻剂治疗各种疾病的治疗和政策提供信息。