Multimodal Probing of Neural Activity Using Transparent Microelectrode Arrays 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 and small spatial coverage due to typically small field-of-view of imaging setups. Furthermore, measures more common in human studies, such as EEG and ECoG, cannot be inferred from optical recordings, leading to a gap between our understanding of dynamics of microscale populations and brain-scale neural activity. Here we propose Neuro-clear as a unique and innovative transparent probe technology to synergistically combine calcium imaging, electrical recording 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, and (ii) Adaptation of multi-layer silicon CMOS fabrication techniques for developing high-density flexible probes with a very small form factor. Graphene electrodes will be nano-engineered to achieve ultra-low impedance and stable single-unit recordings. The flexibility and compactness of the probe will minimize tissue damage and chronic inflammatory response. Neuro-clear will inherit the advantages of silicon neural probes and flexible polymer microelectrode arrays to probe activities of neuronal microcircuits at multiple spatial and temporal scales through crosstalk-free integration of calcium imaging, electrical recording and optogenetics.
Neural circuit dysfunctions are the cause of most neurological diseases, including epilepsy, Parkinson?s disease, dystonia, depression and schizophrenia. Proposed technology can open up exciting avenues to understand mechanisms of neurological disorders and improve therapeutic approaches based on neuromodulation. Understanding circuit dysfunction in these disorders could facilitate development of effective targeted treatments and could greatly impact outcome for many of the one billion people affected by neurological disorders, worldwide.