Optogenetics combined with electrical recording has emerged as a powerful tool for investigating causal relationships between neural circuit activity and function. However, the size of optogenetically manipulated tissue is typically 1-2 orders of magnitude larger than that can be electrically recorded, rendering difficulty for assigning functional roles of recorded neurons. Here we report a viral vector-delivery optrode (VVD-optrode) system for precise integration of optogenetics and electrophysiology in the brain. Our system consists of flexible microelectrode filaments and fiber optics that are simultaneously self-assembled in a nanoliter-scale, viral vector-delivery polymer carrier. The highly localized delivery and neuronal expression of opsin genes at microelectrode-tissue interfaces ensure high spatial congruence between optogenetically manipulated and electrically recorded neuronal populations. We demonstrate that this multifunctional system is capable of optogenetic manipulation and electrical recording of spatially defined neuronal populations for three months, allowing precise and long-term studies of neural circuit functions.

relate neural activity with stimulus and action across multiple timescales-from millisecond-precise spiking patterns that represent sensory and motor information to longer-term neural plasticity that enables neural circuits to progressively adapt to changing environmental contingencies. [2,3] High-density silicon probes and microwire arrays [4][5][6][7] are valuable tools for large-scale recordings of neuronal activity at single-spike resolution and have been applied to show that perceptual learning involves distributed brain regions. [8,9] However, the mechanical mismatch between stiff probes and soft neural tissues can cause micromotion-related inflammatory responses and recording instabilities, [10][11][12] limiting their long-term use in basic and biomedical applications. Flexible probes, including injectable mesh electronics, [13] nano electronic thread, [14] and Neurotassel, [15] have been developed to reduce the mechanical mismatch between probes and tissues. These probes have shown greatly reduced micromotion and inflammatory responses in the brain, thus leading to improved long-term stability in neuronal recordings. However, the bending stiffness of micrometer-thick polymer substrates in these flexible probes is typically two orders of magnitude higher than that of nanofilm electrodes, making it a limiting factor in cellular-scale electrode-tissue interfacings. It is thus highly desirable to develop novel neural electrode technologies [13][14][15][16][17][18][19][20][21][22][23][24][25] that can enable intimate integration with neural tissues and stable tracking of neuronal activity over long terms.In this study, we develop free-standing nanofilm electrode arrays for intimate neural interfacings and stable neuronal activity tracking over long terms. To assist depth implantation into the brain, each NEA was encapsulated into a biodissolvable polymer carrier through elastocapillary selfassembly. After implantation into mouse brain, the high flexibility of free-standing gold nanofilms facilitated their intimate and innervated integration with neural tissues. As a result, chronically implanted NEAs could allow stable tracking of the same populations of neurons over months. This capability allowed us to study how the same neuronal populations in the dorsal striatum represent and update stimulus-outcome associations across multiple timescales during perceptual learning.Flexible neural electrodes integrated on micrometer-thick polymer substrates offer important opportunities for improving the stability of neuronal activity recordings during cognitive processes. However, the bending stiffness of micrometer-thick polymer substrates is typically two orders of magnitude higher than that of nanofilm electrodes, making it a limiting factor in electrode-tissue interfacings. Here, this limitation is overcome by developing self-assembled nanofilm electrode arrays (NEAs) that consist of high-density, free-standing gold nanofilm electrodes. Chronically implanted NEAs can form intimate and innervated interfaces with neural...

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A multifunctional neural device has been developed by integrating microfabricated flexible microelectrodes and electrodeposited NaYF4:Yb3+: Er3+ up-conversion films, allowing simultaneous electrophysiological recording and near-infrared optogenetics.

There are major initiatives around the world with a focus on enabling the "Hydrogen Economy", with the hope that this can become part of a clean, sustainable alternative to fossil fuels. One key aspect of that is the development of proton conducting materials for fuel cells and hydrogen separation membranes. To better understand the design of improved proton conducting ceramics, we have undertaken a study that combines synthesis, neutron scattering and computational investigations. Highly conducting fluorite and perovskite related ceramics have been characterized using quasielastic scattering, powder diffraction, and vibrational spectroscopy at the Spallation Neutron Source. Here we present recent work looking at the use of this combined computational/experimental approach to understand the mechanism of proton conduction, and consider implications on the design of new materials.