Self-assembled multifunctional neural probes for precise integration of optogenetics and electrophysiology

Abstract

Optogenetics combined with electrical recording has emerged as a powerful tool for investigating causal relationships between neural circuit activity and function. However, the size of optogenetically manipulated tissue is typically 1-2 orders of magnitude larger than that can be electrically recorded, rendering difficulty for assigning functional roles of recorded neurons. Here we report a viral vector-delivery optrode (VVD-optrode) system for precise integration of optogenetics and electrophysiology in the brain. Our system consists of flexible microelectrode filaments and fiber optics that are simultaneously self-assembled in a nanoliter-scale, viral vector-delivery polymer carrier. The highly localized delivery and neuronal expression of opsin genes at microelectrode-tissue interfaces ensure high spatial congruence between optogenetically manipulated and electrically recorded neuronal populations. We demonstrate that this multifunctional system is capable of optogenetic manipulation and electrical recording of spatially defined neuronal populations for three months, allowing precise and long-term studies of neural circuit functions.

Multimodal neural probes for combined optogenetics and electrophysiology

“…(2017) Polymer; Laser: 473 nm Polymer Diameter: ∼85 μm Sti: 1 High throughput TDP Flexibility Rec: 1 Long-term stability Jiang et al. (2020) Polymer; Laser: 473 nm Polymer Diameter: ∼250 μm Sti: 1 High throughput TDP Rec: 5, 7 Large spatial coverage Zou et al. (2021) Optical fiber; Laser: 473, 589 nm Polymer Diameter: ∼80–220 μm Sti: 1 High spatial precision Elastocapillary self-assembly Flexibility Rec: 33 Long-term stability …”

“…Recently, Zou et al. developed a self-assembled viral vector delivering (VVD) optrode for precise integration of optogenetics and electrophysiology ( Zou et al., 2021 ). An array of ultraflexible microelectrode filaments (MEFs) and optical fiber were immersed in a viral vector containing PEG melt and then withdrawn into ambient air.…”

“… (H) Percentage of neurons with a decrease or an increase in firing rates during yellow light (589 nm) stimulation. Panels D to H are reproduced from Zou et al. (2021) .…”

Engineering Brain Organoids: Toward Mature Neural Circuitry with an Intact Cytoarchitecture

“…Whole organoid-electronics hybrid was fixed after electrical recording and cleared for in situ sequencing, leading to the explication of spatially-resolved RNA expression at the single-cell level. Optogenetics may enrich the knowledge in this field by manipulating the electrical activity of specific neurons ( 155 , 156 ). Chemo-genetics, represented by DREADDs (designer receptor exclusively activated by designer drugs), may also enable the functional segregation of neuronal subtypes in brain organoids ( 157 , 158 ).…”

Speed Gradient Control Algorithm for Optogenetic Modeling

“…Optogenetic data can be very useful for reconstructing dynamical models of brain dynamics (Oprisan et al, 2015) and for imaging and manipulating brain networks (Forli et al, 2021). Together with electrophysiological data, it provides the selfassembled multifunctional neural probes as a powerful tool for investigating causal relationships between neural circuit activity and function (Zou et al, 2021).…”