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

这项应用，“成像神经元，星形胶质细胞和血管同步，以评估可卡因的影响， 对NIDA的CEBRA计划“开发或改造成瘾的创新技术”做出了回应 研究“。该提案的中心目标是开发一种新型的人工智能（AI）， 荧光和光学多普勒显微镜（AI-flODM）用于神经元Ca 2+的同时成像 (Ca2+N）、星形胶质细胞Ca 2+（Ca 2 +A）活性和脑血流速度（CBFv） 清醒的动物人工智能框架将用于有效地最大限度地减少运动伪影，降噪和分割 时间推移图像，从时空分析将被应用于导出同步的Ca 2 +N， Ca 2 +A和CBFv活性以其静息态低频振荡（LFOs，<1Hz）为特征， 清醒动物的mPFC（目的1）。AI-flODM将用于评估可卡因对Ca 2 +N，Ca 2 +A和Ca 2 + N的影响。 未处理小鼠和暴露于慢性可卡因和化学遗传学（DREADD）的小鼠mPFC中的CBFv LFO 将用于确定Ca 2 +A介导可卡因诱导的Ca 2 +N和CBFv同步化（目的2）。 一个跨学科的研究团队已经组建，包括生物医学工程师，神经成像， 科学家和计算机科学家进行拟议的研究和开发。本申请 将有价值的探索相互作用，星形胶质细胞信号，神经元兴奋性和局部 微血管反应参与mPFC功能和可卡因引起的变化。广大 这种应用的影响将是提供一种工具，以补充其他神经成像方式，以测量 神经元、星形胶质细胞和血管方面的脑功能。

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.