PROJECT SUMMARY This application is submitted in response to the Bioengineering Research Grant’s R01 mechanism. This application proposes to develop a miniaturized head-mounted device that seamlessly integrate wide-field optical imaging and electrocorticogram (ECoG) recordings to achieve multimodal activity mapping of the whole cortex during free behavior. The proposal builds on technological developments in our lab – transparent polymer skulls that provide optical access to an estimated 800,000 to 1,000,000 neurons across 90 mm2 of the surface of the dorsal cortex of the mouse. In AIM 1 we will develop head-mounted imaging systems for mesoscale activity mapping of the whole dorsal cortex in freely moving and behaving mice. In AIM 2, we will engineer transparent polymer skulls integrated with multilayer inkjet-printed electrocorticogram (ECoG) electrode arrays that allows simultaneous optical imaging and cortical surface field potential recordings. We will engineer custom interface electronics integrated into the head-mounted device developed in AIM 1 to enable simultaneous ECoG recordings and cortex wide imaging in freely moving mice. In AIM 3 we will utilize the devices developed in Aims 1 and 2, to study dynamics of cortical activity patterns during novel object recognition and exploration tasks. These developments will enable fundamentally new kinds of experimental studies in the mouse and reveal new insights into the neuronal computations that underlie sensory perception, action and cognitive processes.