Title: Brain-wide mapping of astrocyte dynamics using genetically encoded assembly recorders (GEARs)

Astrocytes are essential elements to the central nervous system and engaged in diverse physiological processes including neurotransmitter clearance, ion homeostasis, hemodynamic control, and synaptic plasticity. Calcium signal in astrocytes serves as a key regulator and has been linked to neural dynamics, synaptic plasticity, hemodynamics, and beyond. Nowadays, in vivo tracking of astrocyte calcium dynamics primarily relies on real-time imaging of genetically encoded calcium sensors like GCaMPs. Despite the high spatiotemporal resolution, the method is limited to tracking a subset of cells within a local brain region. By far, a tool that can map the cellular-level calcium dynamics across the whole brain is still not available. I am committed to filling the technological gap via an intracellular recorder built with protein assemblies, termed Astrocyte-targeted Genetically Encoded Assembly Recorder (astro-GEAR). Resembling tree rings that document climate history, astro-GEAR can write the calcium dynamics in individual astrocytes as fluorescent signals for endpoint readout. It can be globally expressed in astrocytes across the whole brain of behaving animals without affecting their functions. The brain-wide history of astrocyte calcium dynamics can then be retrieved post-mortem via high-throughput imaging. I recently succeeded in developing a neuron-targeted GEAR, which lays the foundation for this project.