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

迷幻物质，人类社会已经知道了几千年，它会导致我们意识状态的深刻改变。尽管在过去的几十年里取得了重大进展，但这些药物的作用方式仍远未被理解。大多数研究集中在这些药物的细胞作用机制上，阐明了所涉及的受体和分子途径。然而，知道孤立的神经元是如何受到影响的，并不能解释药物是如何影响完整的大脑的，因为神经元是高度相互联系的。本项目的目的是进一步了解在经典致幻剂作用下，通过激活血清素能5-HT2A受体，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、宽视场成像和先进的计算方法来检查给药小鼠的大脑活动。该博士生将获得系统和计算神经科学的尖端方法的专业知识，并将有助于促进我们对神经药理学和系统神经科学交叉的基本问题的理解。

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.