PI: Xie, Huikai Proposal: 1512531 Understanding how cellular, physiological, and anatomical changes in the brain alter behavior is one of the great challenges in basic neuroscience. An informative approach to linking brain and behavior is to continuously examine brain structure and function in actively behaving animals. The objective of this project is to develop a novel miniature two-photon microscopy (fTPM) probe and use it to image and gain insight of neural activity and anatomy in awake, freely moving animals.
While fiber-optic two-photon microscopy (fTPM) approaches have shown promise for brain imaging in a natural state, current iterations lack efficient 3D-scanning capabilities and are not amenable for use in mice, the premier model for the mechanistic dissection of neural circuit function in the mammalian brain. The miniaturization of the probe is enabled by a unique electrothermal MEMS actuator design for both lateral and axial laser scanning. Specific tasks are (1) to develop a miniature MEMS-based fiber-optic probe with built-in full 3D scanning capability; (2) to validate the performance of the probe by performing chronic in vivo imaging of fine neural structure in cortical and deep-brain tissue in mice; and (3) to image and analyze neuronal morphology and activity, in awake, freely moving mice over time, using the miniature probe.