Revealing the circuit mechanisms of altered conscious perception with neuropixels recordings and biophysically-inspired neural networks.

通过神经像素记录和生物物理学启发的神经网络揭示改变意识感知的回路机制。

• 批准号: BB/X013243/1
• 负责人: Sean Froudist-Walsh
• 金额: $ 25.39万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Research Grant
• 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=BB%2FX013243%2F1
• 关键词: Revealing; circuit; mechanisms; altered; conscious

Psilocybin is a compound found in 'magic mushrooms' that alters conscious perception. Our goal is to understand how psilocybin changes brain connectivity and conscious perception. To achieve this, we will bring together experts in brain anatomy and function with experts in artificial intelligence. We will first analyse and combine data on the brain's anatomy and function. We will use this data to simulate the effects of psilocybin on the brain's circuits. We can then analyse the simulation to learn how psilocybin changes brain activity and the conscious experience.Psilocybin has exploded in popularity as a recreational drug, a mental health treatment and an aid for creativity. The popularity derives in part from its effects on conscious perception. Conscious perception emerges from activity across scales of brain organisation. We aim to integrate across these scales. In this way, we will learn how the local effects of psilocybin lead to reorganisation of connections across the brain.The nature of the psilocybin experience does not only depend on biological factors. The mental state of the person taking the drug also affects the experience. We need to know how mental states can change psilocybin's effects on neural circuits. This would show how psychological and biological factors influence each other and determine our experience. Both natural chemical transmitters and drugs bind with receptors to open channels in neurons, much as a key fits a lock to open a door. We recently found the receptors that psilocybin binds to in different amounts across different brain areas. We aim to test whether this can explain the powerful influence of psilocybin on conscious perception. We propose to use a new advanced recording technology to measure psilocybin's effects on the activity of hundreds of neurons in the rat brain. We will combine this data with our maps of the locations of receptors in the brain. We will use this data to build a simulation of psilocybin's effects on the brain based on real biology. This will provide a missing link between the psychological and biological effects of psilocybin. Scientists can use this to design and refine future experiments.We have three key objectives:1. To analyse recordings of neural activity from the rat brain to identify how psilocybin's changes brain architecture.2. To simulate how the mental state can combine with biological factors and alter the psilocybin experience3. To simulate how the brain's physiology and anatomy determine psilocybin's ability to alter conscious perception. This project will create an open software platform to advance our understanding of psychedelic drugs. This has the potential to move forward both our fundamental understanding of the brain and drug development.

裸盖菇素是一种在“神奇蘑菇”中发现的化合物，可以改变意识感知。我们的目标是了解裸盖菇素是如何改变大脑连接和意识感知的。为了实现这一目标，我们将把大脑解剖和功能方面的专家与人工智能方面的专家聚集在一起。我们将首先分析和合并有关大脑解剖和功能的数据。我们将使用这些数据来模拟裸盖菇素对大脑回路的影响。然后我们可以分析模拟来了解裸盖菇素是如何改变大脑活动和意识体验的。裸盖菇素作为一种娱乐药物、心理健康治疗和创造力的辅助手段，已经大受欢迎。这种受欢迎程度在一定程度上源于它对意识感知的影响。有意识的知觉产生于大脑组织的各个尺度上的活动。我们的目标是在这些规模上进行整合。通过这种方式，我们将了解裸盖菇素的局部效应如何导致整个大脑连接的重组。裸盖菇素体验的性质不仅取决于生物因素。吸毒者的精神状态也会影响这种体验。我们需要知道精神状态如何改变裸盖菇素对神经回路的影响。这将表明心理和生物因素是如何相互影响并决定我们的体验的。天然化学递质和药物都与受体结合，打开神经元中的通道，就像钥匙打开门的锁一样。我们最近发现裸盖菇素在不同的大脑区域以不同的数量与之结合的受体。我们的目标是测试这是否可以解释裸盖菇素对意识知觉的强大影响。我们建议使用一种新的先进记录技术来测量裸盖菇素对大鼠大脑中数百个神经元活动的影响。我们将把这些数据与我们的大脑受体位置图结合起来。我们将使用这些数据来建立一个基于真实生物学的裸盖菇素对大脑影响的模拟。这将在裸盖菇素的心理和生物效应之间提供一个缺失的环节。科学家可以利用这一点来设计和改进未来的实验。我们有三个关键目标：1.分析大鼠大脑的神经活动记录，以确定裸盖菇素是如何改变大脑结构的。模拟精神状态如何与生物因素结合并改变裸盖菇素的体验。来模拟大脑的生理和解剖结构如何决定裸盖菇素改变意识感知的能力。该项目将创建一个开放的软件平台，以促进我们对迷幻药物的理解。这有可能推动我们对大脑和药物开发的基本理解。

项目成果

Gradients of neurotransmitter receptor expression in the macaque cortex.

• DOI: 10.1038/s41593-023-01351-2
• 发表时间: 2023-07
• 期刊: NATURE NEUROSCIENCE
• 影响因子: 25
• 作者: Froudist-Walsh, Sean;Xu, Ting;Niu, Meiqi;Rapan, Lucija;Zhao, Ling;Margulies, Daniel S. S.;Zilles, Karl;Wang, Xiao-Jing;Palomero-Gallagher, Nicola
• 通讯作者: Palomero-Gallagher, Nicola

Cell type-specific connectome predicts distributed working memory activity in the mouse brain.

• DOI: 10.7554/elife.85442
• 发表时间: 2024-01-04
• 期刊: eLife
• 影响因子: 7.7
• 作者: Ding X;Froudist-Walsh S;Jaramillo J;Jiang J;Wang XJ
• 通讯作者: Wang XJ