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By integrating optical stimulation, electrophysiological recording, and neurochemical sensing, these multifunctional interfaces offer novel ways to interrogate brain circuits in vivo. However, the greater the integration, the more sophisticated and consequently challenging the front\u2010end of the implantable system becomes. The challenge revolves around three bottlenecks: (i) complexity of high\u2010density optoelectrical integration, (ii) adverse long\u2010term foreign body response (FBR), and (iii) limited incorporation of sensors for both cellular and biomolecular activity, including neurotransmitter activity and dynamics. Here we focus on the strategies to address these challenges in the context of device engineering at its interface with tissue. First, we present platforms developed by the scientific community for interacting with neural cells via electrical and optical means to achieve high resolution. 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