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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.

迷幻物质是人类社会几千年来都知道的，它会导致我们意识状态的深刻变化。尽管在过去几十年里取得了重大进展，但人们对这些药物的运作方式还远不清楚。大多数研究集中在这类药物的细胞作用机制上，阐明了涉及的受体和分子途径。然而，知道神经元在孤立地考虑时是如何受到影响的，并不能解释药物如何影响完整的大脑，在那里神经元是高度相互联系的。本项目的目的是从系统水平进一步了解5-羟色胺能5-HT2A受体激活引起的经典迷幻药作用下大脑皮质活动的变化。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、宽视野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。博士生将在系统和计算神经科学的尖端方法方面获得专业知识，并将帮助我们加深对神经药理学和系统神经科学交叉点上的一个基本问题的理解。