Strategies for optical control and simultaneous electrical readout of extended cortical circuits

Abstract

Background To dissect the intricate workings of neural circuits, it is essential to gain precise control over subsets of neurons while retaining the ability to monitor larger-scale circuit dynamics. This requires the ability to both evoke and record neural activity simultaneously with high spatial and temporal resolution. New Method In this paper we present approaches that address this need by combining micro-electrocorticography (μECoG) with optogenetics in ways that avoid photovoltaic artifacts. Results We demonstrate that variations of this approach are broadly applicable across three commonly studied mammalian species—mouse, rat, and macaque monkey—and that the recorded μECoG signal shows complex spectral and spatio-temporal patterns in response to optical stimulation. Comparison with existing methods While optogenetics provides the ability to excite or inhibit neural subpopulations in a targeted fashion, large-scale recording of resulting neural activity remains challenging. Recent advances in optical physiology, such as genetically encoded Ca2+ indicators, are promising but currently do not allow simultaneous recordings from extended cortical areas due to limitations in optical imaging hardware. Conclusions We demonstrate techniques for the large-scale simultaneous interrogation of cortical circuits in three commonly used mammalian species.

Advanced Electrical and Optical Microsystems for Biointerfacing

“…Current transparent microelectrodes for electrophysiology include ITO, [ 235 ] graphene, [ 236,237 ] CNTs, [ 238 ] metallic NWs, [ 239 ] metal grids, [ 240 ] and their hybrid composites. [ 241,242 ] ITO exhibits excellent transparency across the visible spectrum (85–95%) and low sheet resistance (4–40 Ω sq −1 ).…”

“…[ 251 ] Recently, Ledochowitsch et al demonstrated micro‐ECoG (μ‐ECoG) arrays that consisted of 96 ITO (thickness 110 nm) microelectrodes on a 3 μm transparent parylene substrate for electrical readout of cortical circuits under external optogenetic stimulation. [ 235 ] The ITO microelectrodes (diameter 40 μm) exhibit an average transmittance > 90% across the visible spectrum and an electrochemical impedance <1 MΩ at 1 kHz. The ITO MEAs successfully recorded optogenetically evoked auditory responses at the stimulation sites in transgenic mice.…”

Transparent and flexible ECoG electrode arrays based on silver nanowire networks for neural recordings

“…There have been promising attempts to build transparent ECoG electrodes using tin doped indium oxide (ITO) and graphene. An array with 49 ITO electrodes (500 μm diameter) was tested in vivo (P Ledochowitsch et al, 2015). Thunemann et al have recently reported the use of graphene in ECoG electrodes (Thunemann et al, 2018).…”

Real-time spike sorting platform for high-density extracellular probes with ground-truth validation and drift correction

“…However, unlike optical recordings that provide cell type information, up to now the weakness of extracellular recordings has been a lack of exact cell type information. There are now efforts to relate electrical activity patterns that are specific to genetically identifiable cell populations [25][26][27] . JRCLUST's ability to cluster unit activities could be extended to identify specific cell types through use of such devices and the generation of ground truth data inclusive of cell type metadata.…”