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

Liang Zou,Jinfen Wang,Shouliang Guan,Lei Gao,Ying Fang,Jianfei Ding,Huihui Tian

doi:10.1038/s41467-021-26168-0

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.

Highlights

Optogenetics combined with electrical recording has emerged as a powerful tool for investigating causal relationships between neural circuit activity and function
We describe a multifunctional system for longterm optogenetic stimulation and multi-channel electrical recording of spatially defined neuronal populations in the brain
We demonstrate that our multifunctional probes enable optogenetic inhibition of electrically recorded neuronal populations with substantially improved precision compared to conventional methods (91% versus 24%)

Summary

Introduction

Optogenetics combined with electrical recording has emerged as a powerful tool for investigating causal relationships between neural circuit activity and function. 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. Addressing this goal requires tools that can selectively manipulate the activity of specific types of cells to assess their roles in neural circuit functions This has been made possible by recent advances in genetic and optical technologies[1]. Combining optogenetic stimulation with multi-channel electrical recording can allow for simultaneous cell-type-specific control and spatiotemporal readout of neural activity, constituting a powerful tool for the analysis of causal relationships between neural circuit activity and function[7,8,9]. The implementation of combined optogenetics/electrophysiology techniques depends on prior delivery and expression of opsin genes in specific types of cells, mostly through stereotaxic injection of viral vectors into a targeted brain region[10].

Methods

Results

Conclusion