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

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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.