Multichannel optogenetics combined with laminar recordings for ultra-controlled neuronal interrogation

David Eriksson,Kirti Sharma,Anupriya Thirumalai,Artur Schneider,Mansour Alyahyay,Ilka Diester,Brice de la Crompe,Patrick Ruther

doi:10.1038/s41467-022-28629-6

Abstract

Simultaneous large-scale recordings and optogenetic interventions may hold the key to deciphering the fast-paced and multifaceted dialogue between neurons that sustains brain function. Here we have taken advantage of thin, cell-sized, optical fibers for minimally invasive optogenetics and flexible implantations. We describe a simple procedure for making those fibers side-emitting with a Lambertian emission distribution. Here we combined those fibers with silicon probes to achieve high-quality recordings and ultrafast multichannel optogenetic inhibition. Furthermore, we developed a multi-channel optical commutator and general-purpose patch-cord for flexible experiments. We demonstrate that our framework allows to conduct simultaneous laminar recordings and multifiber stimulations, 3D optogenetic stimulation, connectivity inference, and behavioral quantification in freely moving animals. Our framework paves the way for large-scale photo tagging and controlled interrogation of rapid neuronal communication in any combination of brain areas.

Highlights

Simultaneous large-scale recordings and optogenetic interventions may hold the key to deciphering the fast-paced and multifaceted dialogue between neurons that sustains brain function
We propose an alternative optrode design for silicon probes based on multiple ultrathin optical fibers, which we call Fused Fiber Light Emission and eXtracellular Recordings (FFLEXR)
To allow simultaneous extracellular recordings and multichannel fiber targeting in a freely moving animal, we developed an optical commutator that is integrated into an electrical commutator (Fig. 1A)

Summary

Introduction

Simultaneous large-scale recordings and optogenetic interventions may hold the key to deciphering the fast-paced and multifaceted dialogue between neurons that sustains brain function. Combined optogenetic manipulations and electrophysiological recordings have been pioneered with a twotipped optrode[1] and optetrodes, i.e., an optical fiber surrounded by tetrodes[2] This has been refined with a single-tip approach[3], integrated fibers in electrode arrays[4], and the use of micro light-emitting diodes (μ-LEDs) combined with recording probes or co-integrated in silicon-based probes[5,6,7,8]. We mitigate the above-mentioned issues with thin, linearly emitting optical fibers that can be attached to any silicon probe, depth-resolved stimulation, a lightweight fiber-matrix connector, a flexible multifiber ribbon cable, an optical commutator for efficient multichannel stimulation, a general-purpose patch cord, and a photovoltaic response (PVR) management algorithm

Methods

Results

Conclusion