Transparent neural interfaces: challenges and solutions of microengineered multimodal implants designed to measure intact neuronal populations using high-resolution electrophysiology and microscopy simultaneously

The aim of this review is to present a comprehensive overview of the feasibility of using transparent neural interfaces in multimodal in vivo experiments on the central nervous system. Multimodal electrophysiological and neuroimaging approaches hold great potential for revealing the anatomical and functional connectivity of neuronal ensembles in the intact brain. Multimodal approaches are less time-consuming and require fewer experimental animals as researchers obtain denser, complex data during the combined experiments. Creating devices that provide high-resolution, artifact-free neural recordings while facilitating the interrogation or stimulation of underlying anatomical features is currently one of the greatest challenges in the field of neuroengineering. There are numerous articles highlighting the trade-offs between the design and development of transparent neural interfaces; however, a comprehensive overview of the efforts in material science and technology has not been reported. Our present work fills this gap in knowledge by introducing the latest micro- and nanoengineered solutions for fabricating substrate and conductive components. Here, the limitations and improvements in electrical, optical, and mechanical properties, the stability and longevity of the integrated features, and biocompatibility during in vivo use are discussed.