Tapered Fibers Combined With a Multi-Electrode Array for Optogenetics in Mouse Medial Prefrontal Cortex.

Leonardo Sileo,Massimo De Vittorio,Tobias Holzhammer,Jastyn A Pöpplau,Sebastian H Bitzenhofer,Marco Pisanello,Ileana L Hanganu-Opatz,Ferruccio Pisanello,Patrick Ruther,Emanuela Maglie,Filippo Pisano,Elisa Bellistri,Barbara Spagnolo

doi:10.3389/fnins.2018.00771

Abstract

Optogenetics offers many advantages in terms of cell-type specificity, allowing to investigate functional connectivity between different brain areas at high spatial and neural population selectivity. In order to obtain simultaneous optical control and electrical readout of neural activity, devices called “optrodes” are employed. They are typically composed of a linear array of microelectrodes integrated on a slender probe shafts combined with flat-cleaved optical fibers (FF) placed above the recording sites. However, due to tissue absorption and scattering, light delivered by the FF unevenly illuminates the region of interest. This issue is of particular relevance when cellular populations are disposed along the dorso-ventral axis, such as in medial prefrontal cortex (mPFC) where cortical layers are aligned vertically. The study presented here aims at using tapered optical fibers (TFs) in combination with a 16-electrode neural probe to better access neural populations distributed along the dorso-ventral axis in the mPFC of newborn mice, restricting light delivery over a specific portion of the cortical layer of interest. Half of the TF surface is coated with a reflecting metal blocking the light to enable light delivery from one side of the probe’s shaft only, with the probe base being designed to host the fiber without interfering with the wire-bonds that connect the recording sites to a printed circuit board. Monte-Carlo simulations have been implemented to define the relative TF-probe position and to identify the light intensity distribution above the recording sites. In vivo recordings indicate that simultaneous optical stimulation and electrical readout of neural activity in the mPFC benefit from the use of the engineered TF-based optrode in terms of a more uniform light distribution along the dorso-ventral axis and the possibility of restricting light delivery to a subset of electrical recording sites of interest.

Highlights

With the increasing use of optogenetics to investigate functional connectivity in the mouse brain, the development of implantable devices for the simultaneous optical control and electrical monitoring of neural activity has been a major research focus in recent years (Grosenick et al, 2015; Cho et al, 2016; Pisanello et al, 2016)
In this work we propose an optrode design thought to better distribute light on cellular populations distributed in the dorsoventral direction and to restrict illumination to subregions of the medial prefrontal cortex (mPFC)
It is based on a half-coated tapered optical fibers (TFs) placed beside a 16-electrode silicon-based neural probe, whose relative position allows for delivering light to brain tissue addressed by a subset of the 16 recording sites

Summary

Introduction

With the increasing use of optogenetics to investigate functional connectivity in the mouse brain, the development of implantable devices for the simultaneous optical control and electrical monitoring of neural activity has been a major research focus in recent years (Grosenick et al, 2015; Cho et al, 2016; Pisanello et al, 2016). The above-mentioned technologies based in microsystems engineering can help in challenging this issue by placing multiple emitters very close to the individual recording sites These discrete sets of light delivery points face different pitfalls, such as a potential tissue heating induced by Joule’s effects for μLEDs, limited outcoupling efficiencies of diffraction gratings and the high commercialization costs to make these probes available to neuroscience labs. This is possible by exploiting two main features of these devices: (i) the narrowing waveguide allows to exploit mode division demultiplexing to deliver light gradually along a specific segment of the taper (Pisanello et al, 2018); as the taper narrows, the number of guided modes supported by the waveguide decreases, with modes not allowed to propagate toward the tip being outcoupled around the taper, and (ii) the possibility of using metal coatings to mask emission and to direct light to specific sites and directions (Pisano et al, 2018)

Methods

Results

Conclusion