Abstract
Maximizing the potential of optogenetic approaches in deep brain structures of intact animals requires optical manipulation of neurons at high spatial and temporal resolutions, while simultaneously recording electrical data from those neurons. Here, we present the first fiber-less optoelectrode with a monolithically integrated optical waveguide mixer that can deliver multicolor light at a common waveguide port to achieve multicolor modulation of the same neuronal population in vivo. We demonstrate successful device implementation by achieving efficient coupling between a side-emitting injection laser diode (ILD) and a dielectric optical waveguide mixer via a gradient-index (GRIN) lens. The use of GRIN lenses attains several design features, including high optical coupling and thermal isolation between ILDs and waveguides. We validated the packaged devices in the intact brain of anesthetized mice co-expressing Channelrhodopsin-2 and Archaerhodopsin in pyramidal cells in the hippocampal CA1 region, achieving high quality recording, activation and silencing of the exact same neurons in a given local region. This fully-integrated approach demonstrates the spatial precision and scalability needed to enable independent activation and silencing of the same or different groups of neurons in dense brain regions while simultaneously recording from them, thus considerably advancing the capabilities of currently available optogenetic toolsets.
Highlights
Neural circuits in the brain are intricately woven to govern complex signal pathways responsible for thought, memory, emotion and behavior
Since a GRIN lens has a continuous change of the refractive index (RI) within the lens material, light rays can be continuously bent within the lens until they are focused on a spot
Primary GRIN design equations are: RI at radius r, N (r) = N o[1 − (A/2)r2]27; mechanical length, Z = 2πP/ A 27; numerical aperture, NA =no sin θa, where No is the RI at the lens central axis (1.65); √A is the designed index gradient constant, which depends on lens material and wavelength; P is a lens pitch; no is the RI of surrounding medium around GRIN; and θa is the lens acceptance angle (25 degrees)
Summary
Neural circuits in the brain are intricately woven to govern complex signal pathways responsible for thought, memory, emotion and behavior. We demonstrated a complete multi-site/multi-color optical stimulation and electrical recording system using light sources (LED chips and/or laser diode can mounts) attached to commercial silicon recording probes and/or wire tetrodes[24] While this approach offers multicolor light stimulation, light delivery cannot be achieved at a common site and the assembly procedure is labor-intensive and prone to inaccuracies. Another approach involved the direct assembly of laser chips on a silicon probe back-end[25]; that effort provided a monochromatic (650 nm) optogenetic tool with integrated SU-8 waveguides, yet in vivo testing was not reported and device heating was not addressed. Such experiments may involve (1) independent activation and silencing of a single cell type; (2) activation of one source of inputs to a given cell while silencing a second source; and (3) independent activation (or silencing) of two spatially intermingled cell types
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