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

• 批准号: 2881045
• 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

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.

数千年人类社会已知的迷幻物质导致我们意识状态的深刻改变。尽管在过去的几十年中，这些药物的运作方式远非被理解。大多数研究都集中在此类药物作用的细胞机制上，阐明了所涉及的受体和分子途径。但是，在孤立考虑时，知道神经元如何影响神经元并不能解释该药物如何影响神经元高度互连的完整大脑。本项目的目的是通过激活血清素能5-HT2A受体的激活来进一步了解在经典迷幻作用下对皮质活动变化的理解。我们的具体目标是将单个神经元水平的5-HT2A激动剂在脑活动水平上产生的自发活性的变化与脑活动的变化联系起来。为此，我们将使用高密度的多电极阵列，广场成像和先进的计算方法来检查给定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方面的最先进方法方面获得专业知识，并将帮助我们促进我们对神经药理学与系统神经科学相交的基本问题的理解。