Optimization and distribution of high density cellular scale carbon and silicon arrays

University Of Michigan At Ann Arbor, Ann Arbor MI

Investigators

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Abstract

Project Summary A longstanding goal in neuroscience is to understand the brain at the level of individual neurons. Existing techniques involve inserting electrodes that heavily damage the area that they are recording. Due to the damage it has also been very difficult to combine electrophysiology techniques with imaging the same neurons after the fact. We have developed novel carbon fiber electrode arrays, with individual elements that are 8 ?m in diameter, smaller than most neuron cell bodies. We insert them in linear regularly spaced arrays, record for many weeks, and then slice the brain with the electrodes in place to reconstruct the position of the electrode tips when staining the cells. Using these methods, neurons appear at 88% of neural density, 11 and 13 weeks after implant, within 25 ?m of our functional probes. In the past two years, we have done significant in vivo recording, including of dopamine using FSCV, using 16 channel arrays and made significant progress in fabricating 64 channel devices at high yield, as shown in preliminary data. In the optimization phase, we will complete the following 3 aims: Aim 1) Increase channel count and longevity of the probes by optimizing the manufacturing process. To enable distribution, we will optimize our stiffening techniques for easier comb stacking, automate both deposition of silver epoxy and placement of the carbon fibers, stress test the longevity of the devices, and finally eliminate the wirebonding as the final ?by hand? processing step and cost driver. Aim 2) Deploy arrays for in vivo alpha and beta testing in 6 collaborating neuroscience labs. The Berke lab will continue to be the alpha tester for all device variants, while 5 other labs will serve as beta testers (Stryker, Ganguly, Nelson, Becker, and Garris), using progressively better devices as available from Aim 1, starting with existing devices in Year 1. Aim 3) Enable the broader community to use slice-in-place staining by establishing, distributing, and training people in known working protocols. Beyond NeuN and CD11, we will expand the list of working slice-in-place protocols to include many markers of micro-regions, cortical layers, and Brainbow for connectomics at the level of synapses. We will distribute batches of antibodies known to work well with our slicing and staining techniques through the company Kerafast, as we do now with Brainbow. We will also have 2 summer training sessions in Years 2-3 in all aspects of the slice-in- place recording. At the end of this project, implanting cellular scale electrode arrays and slicing the brain with these electrodes in place after recording will be common practice in half a dozen active neuroscience labs.