Optimization of Transparent Microelectrode Arrays for Large-scale Multimodal Monitoring of Neural Activity - The last decades have witnessed substantial progress in optical technologies revolutionizing our ability to record and manipulate neural activity. However, current cellular-resolution optical recording techniques have several limitations such as low temporal resolution due to slow kinetics of indicators and low frame acquisition rates of imaging setups. Furthermore, measures more common in human studies, such as local field potentials (LFPs) and electrocorticography (ECoG), cannot be inferred from optical recordings, leading to a gap between our understanding of the dynamics of microscale populations and brain-scale neural activity. Here we propose ultra-high density neuro-clear as a unique and innovative transparent probe technology to synergistically combine high-resolution optical imaging, electrophysiological recordings, and optogenetics for large-scale recording and modulation of neural activity. Neuro-clear will consist of planar and laminar probes based on two key technology innovations: (i) Transparent graphene electrodes and wires allowing for efficient light delivery without blocking the field-of-view of the microscope, and elimination of light-induced artifacts in the recordings, (ii) Adaptation of multi-layer silicon CMOS fabrication techniques for developing high-density flexible probes with a very small form factor, and (iii) Integration of data acquisition chips on polymer substrates to achieve minimalist SWaP (size, weight, and power) form factors suitable for head-mounted operation over extended recording sessions. Graphene electrodes will be nano-engineered to achieve ultra-low impedance and stable single-unit recordings. Neuro-clear will inherit the advantages of silicon neural probes and flexible polymer microelectrode arrays to probe the activities of neuronal microcircuits at multiple spatial and temporal scales through crosstalk-free integration of optical imaging, electrical recording, and optogenetics. Such a capability will enable in vivo studies of neural mechanisms responsible for complex behaviors that cannot be understood with existing technologies. Neuro-clear technology will be broadly applicable to problems in neuroscience and will transform neuroscientists' ability to study neural circuits.
