Imaging neural, astrocytic and vascular synchronization to assess cocaine's effects on mPFC

对神经、星形细胞和血管同步进行成像以评估可卡因对 mPFC 的影响

• 批准号: 10586794
• 负责人: Congwu Du
• 金额: $ 18.67万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10586794
• 关键词: 3-Dimensional; Affect; Animals; Artificial Intelligence; Astrocytes; Biomedical Engineering; Blood Flow Velocity; Blood Vessels; Blood capillaries; Brain; Cells; Cerebrovascular Circulation; Cerebrovascular system; Chronic; Cocaine; Complement; Computers; Development; Drug Addiction; Exposure to; Fluorescence; Frequencies; Functional disorder; Genetic; Goals; Image; Imaging Techniques; Interdisciplinary Study; Measures; Medial; Mediating; Mediation; Microscope; Modality; Morphologic artifacts; Motion; Mus; National Institute of Drug Abuse; Neuroglia; Neurons; Neurosciences; Noise; Optical Coherence Tomography; Optics; Prefrontal Cortex; Public Health; Reaction; Research; Resolution; Rest; Role; Scientist; Signal Transduction; Techniques; Translational Research; Viral; addiction; awake; cerebral capillary; cerebral hemodynamics; clinically relevant; cocaine exposure; denoising; designer receptors exclusively activated by designer drugs; detection sensitivity; fluorescence imaging; frontal lobe; imaging platform; in vivo optical imaging; innovation; insight; microscopic imaging; neuroimaging; neuronal excitability; neuronal metabolism; neurovascular coupling; novel; prevent; programs; research and development; response; spatiotemporal; tool

This application, "Imaging neuronal, astrocytic and vascular synchronization to assess cocaine’s effects on mPFC", responds to NIDA’s CEBRA program to ‘develop or adapt innovative techniques for addiction research’. The central goal of this proposal is to develop a novel artificial intelligence (AI) enhanced fluorescence and optical Doppler microscope (AI-flODM) for simultaneous imaging of neuronal Ca2+ (Ca2+N) , astrocytic Ca2+ (Ca2+A) activities and cerebral blood flow velocity (CBFv) in medial prefrontal cortex of awake animals. AI frameworks will be used to effectively minimize motion artifacts, denoise and segment time-lapse images, from which spatiotemporal analyses will be applied to derive the synchronized Ca2+N, Ca2+A, and CBFv activities characterized by their resting-state low-frequency oscillations (LFOs, <1Hz) in mPFC of awake animals (Aim 1). AI-flODM will be used to assess cocaine’s effects on Ca2+N, Ca2+A, and CBFv LFOs in mPFC of naïve mice and mice exposed to chronic cocaine, and chemogenetics (DREADDs) will be used to determine Ca2+A in mediating cocaine-induced Ca2+N and CBFv synchronization (Aim 2). An interdisciplinary research team has been assembled, including biomedical engineers, neuroimaging scientists, and computer scientists to conduct the proposed research and development. This application will be valuable for exploring the interactions in astrocytic signaling, neuronal excitability and local microvascular responses involved in mPFC function and in their changes elicited by cocaine. The broad impact of this application will be to provide a tool to complement other neuroimaging modalities to measure neuronal, astrocytic, and vascular aspects of brain function in awake animals.

该应用程序“对神经、星形细胞和血管同步进行成像以评估可卡因的影响” mPFC”，响应 NIDA 的 CEBRA 计划“开发或调整成瘾创新技术” 该提案的中心目标是开发一种新型人工智能（AI）增强型。 用于神经元 Ca2+ 同时成像的荧光和光学多普勒显微镜 (AI-flODM) 内侧前额皮质 (Ca2+N)、星形细胞 Ca2+ (Ca2+A) 活动和脑血流速度 (CBFv) 清醒动物的人工智能框架将用于有效地减少运动伪影、降噪和分割。 延时图像，从中应用时空分析来导出同步的 Ca2+N， Ca2+A 和 CBFv 活动的特征是其静息态低频振荡（LFO，<1Hz） 清醒动物的 mPFC（目标 1）将用于评估可卡因对 Ca2+N、Ca2+A 和的影响。 初次接触小鼠和暴露于慢性可卡因的小鼠 mPFC 中的 CBFv LFO 和化学遗传学 (DREADD) 将用于确定 Ca2+A 介导可卡因诱导的 Ca2+N 和 CBFv 同步（目标 2）。 已经组建了一个跨学科研究团队，包括生物医学工程师、神经影像学工程师 科学家和计算机科学家进行拟议的研究和开发。 对于探索星形胶质细胞信号、神经兴奋性和局部的相互作用非常有价值 微血管反应涉及 mPFC 功能及其由可卡因引起的变化。 该应用程序的影响将是提供一种工具来补充其他神经成像模式来测量 清醒动物脑功能的神经元、星形细胞和血管方面。