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Linking microscale and macroscale changes in brain activity under the influence of psychedelics

将迷幻药影响下大脑活动的微观和宏观变化联系起来

基本信息

批准号：
2881045
负责人：
金额：
--
依托单位：
University of Sheffield
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2023
资助国家：
英国
起止时间：
2023 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2881045
关键词：
Linking microscale macroscale changes brain

项目摘要

Psychedelic substances, known to human societies for millennia, result in profound alterations of our state of consciousness. The way these drugs operate is far from understood, although in the last few decades significant progress has been made. Most of the research focused on the cellular mechanisms of action of such drugs, elucidating the receptors and molecular pathways that are involved. However, knowing how a neuron is affected when considered in isolation does not explain how the drug affects the intact brain, where neurons are highly interconnected. The aim of the present project is to further the systems-level understanding of the changes in cortical activity under the effect of classical psychedelics, exerted by activation of serotonergic 5-HT2A receptors. Our specific objective is to link the changes in spontaneous activity produced by 5-HT2A agonists at the level of single neurons to macroscale changes in brain activity. Towards this end, we will use high-density multi-electrode arrays, widefield imaging and advanced computational methods to examine brain activity in mice given psychedelic drugs. The PhD student will gain expertise in cutting-edge methods in systems and computational neuroscience and will help advance our understanding of a fundamental question at the intersection of neuropharmacology and systems neuroscience.

迷幻物质为人类社会所知已有数千年之久，它会导致我们的意识状态发生深刻的改变。尽管在过去几十年中已经取得了重大进展，但这些药物的作用方式尚不清楚。大多数研究集中于此类药物的细胞作用机制，阐明所涉及的受体和分子途径。然而，单独考虑时了解神经元如何受到影响并不能解释药物如何影响完整的大脑，因为神经元在大脑中是高度互连的。本项目的目的是进一步从系统层面理解经典致幻剂作用下皮质活动的变化，这些变化是通过激活血清素能 5-HT2A 受体而产生的。我们的具体目标是将 5-HT2A 激动剂在单个神经元水平上产生的自发活动的变化与大脑活动的宏观变化联系起来。为此，我们将使用高密度多电极阵列、宽场成像和先进的计算方法来检查服用迷幻药物的小鼠的大脑活动。博士生将获得系统和计算神经科学前沿方法的专业知识，并将有助于加深我们对神经药理学和系统神经科学交叉点的基本问题的理解。