These technologies have shown great promise for simultaneous electrical recordings and optical stimulation in vivo. Approaches to integrating optical and electrical modalities have ranged from adding fiber optics to existing Utah arrays to the Optetrode or other integrated electro-optical coaxial structures 13– 17. It is also fundamental for determining the mechanistic basis of sensorimotor disorders, defining how circuit activity is affected by injury, and how it might be restored or facilitated. The ability to bi-directionally interface with genetically defined neuron types and circuits is key to ultimately being able to understand how the nervous system computes and controls behavior. The ideal neural probe would combine optical and electrical modes while maintaining small cross-sectional dimensions and tunable lengths. However, given the strong light scattering and high absorption properties of neural tissue, optogenetic interfacing with deep neural circuits typically requires the implantation of large-diameter rigid fibers, which can make this approach more invasive than its electrical counterpart 10– 12. Optogenetic techniques enable high-speed modulation of cellular activity through targeted expression and activation of light-sensitive opsins 9. Although these probes have advanced the field of neural interfacing, next-generation devices should enable targeted stimulation in addition to colocalized electrical recordings 3, 8. State-of-the-art Neuropixel and carbon fiber probes have improved on these previous devices by increasing electrode density and reducing probe dimensions and rigidity 5– 7.
However, their large footprint and rigidity lead to tissue damage and inflammation that hamper long-term recordings 3, 4. Microelectrode arrays, such as the Utah or Michigan arrays, have allowed tracking of distributed neural activity with millisecond precision 1, 2.
Microelectrode recordings are the gold standard for measuring individual neurons’ activity at high temporal resolution in any nervous system region and are central to defining the role of neural circuits in controlling behavior. Given their negligible inflammatory response, these probes promise to enable a new generation of readily tunable multi-modal devices for long-term, minimally invasive interfacing with neural circuits. Scalable fabrication strategies can be used with various electrical and optical materials, making the probes highly customizable to experimental requirements, including length, diameter, and mechanical properties. In the brain, the probes allowed robust electrical measurement and optogenetic stimulation. Here a multi-modal coaxial microprobe design with a minimally invasive footprint (8–14 µm diameter over millimeter lengths) that enables efficient electrical and optical interrogation of neural networks is presented. However, reductions in the size of multi-modal interfaces are needed to further improve biocompatibility and long-term recording capabilities. Recent devices have focused on matching the mechanical compliance of tissue to reduce inflammatory responses. Central to advancing our understanding of neural circuits is developing minimally invasive, multi-modal interfaces capable of simultaneously recording and modulating neural activity.
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