Automated in vivo patch-clamp evaluation of extracellular multielectrode array spike recording capability.

Much innovation is currently aimed at improving the number, density, and geometry of electrodes on extracellular multielectrode arrays for in vivo recording of neural activity in the mammalian brain. To choose a multielectrode array configuration for a given neuroscience purpose, or to reveal design principles of future multielectrode arrays, it would be useful to have a systematic way of evaluating the spike recording capability of such arrays. We describe an automated system that performs robotic patch-clamp recording of a neuron being simultaneously recorded via an extracellular multielectrode array.

Heterogeneous neural amplifier integration for scalable extracellular microelectrodes.

We here demonstrate multi-chip heterogeneous integration of microfabricated extracellular recording electrodes with neural amplifiers, highlighting a path to scaling electrode channel counts without the need for more complex monolithic integration. We characterize the noise and impedance performance of the heterogeneously integrated neural recording electrodes, and analyze the design parameters that enable the low-voltage neural input signals to co-exist with the high-frequency and high-voltage digital outputs on the same silicon substrate. This heterogeneous integration approach can enable future scaling efforts for microfabricated neural probes, and provides a design path for modular, fast, and independent scaling innovations in recording electrodes and neural amplifiers.

Processes for design, construction and utilisation of arrays of light-emitting diodes and light-emitting diode-coupled optical fibres for multi-site brain light delivery.

Optogenetics enables light to be used to control the activity of genetically targeted cells in the living brain. Optical fibers can be used to deliver light to deep targets, and LEDs can be spatially arranged to enable patterned light delivery. In combination, arrays of LED-coupled optical fibers can enable patterned light delivery to deep targets in the brain.

Close-Packed Silicon Microelectrodes for Scalable Spatially Oversampled Neural Recording.

Objective: Neural recording electrodes are important tools for understanding neural codes and brain dynamics. Neural electrodes that are closely packed, such as in tetrodes, enable spatial oversampling of neural activity, which facilitates data analysis. Here we present the design and implementation of close-packed silicon microelectrodes to enable spatially oversampled recording of neural activity in a scalable fashion.

A direct-to-drive neural data acquisition system.

Driven by the increasing channel count of neural probes, there is much effort being directed to creating increasingly scalable electrophysiology data acquisition (DAQ) systems. However, all such systems still rely on personal computers for data storage, and thus are limited by the bandwidth and cost of the computers, especially as the scale of recording increases. Here we present a novel architecture in which a digital processor receives data from an analog-to-digital converter, and writes that data directly to hard drives, without the need for a personal computer to serve as an intermediary in the DAQ process.

Optogenetics and thermogenetics: technologies for controlling the activity of targeted cells within intact neural circuits.

In recent years, interest has grown in the ability to manipulate, in a temporally precise fashion, the electrical activity of specific neurons embedded within densely wired brain circuits, in order to reveal how specific neurons subserve behaviors and neural computations, and to open up new horizons on the clinical treatment of brain disorders. Technologies that enable temporally precise control of electrical activity of specific neurons, and not these neurons' neighbors-whose cell bodies or processes might be just tens to hundreds of nanometers away-must involve two components. First, they require as a trigger a transient pulse of energy that supports the temporal precision of the control.

Optogenetic tools for analyzing the neural circuits of behavior.

In order to understand how the brain generates behaviors, it is important to be able to determine how neural circuits work together to perform computations. Because neural circuits are made of a great diversity of cell types, it is critical to be able to analyze how these different kinds of cell work together. In recent years, a toolbox of fully genetically encoded molecules has emerged that, when expressed in specific neurons, enables the electrical activity of the targeted neurons to be controlled in a temporally precise fashion by pulses of light.

A wirelessly powered and controlled device for optical neural control of freely-behaving animals.

Optogenetics, the ability to use light to activate and silence specific neuron types within neural networks in vivo and in vitro, is revolutionizing neuroscientists' capacity to understand how defined neural circuit elements contribute to normal and pathological brain functions. Typically, awake behaving experiments are conducted by inserting an optical fiber into the brain, tethered to a remote laser, or by utilizing an implanted light-emitting diode (LED), tethered to a remote power source. A fully wireless system would enable chronic or longitudinal experiments where long duration tethering is impractical, and would also support high-throughput experimentation.

Millisecond-timescale optical control of neural dynamics in the nonhuman primate brain.

To understand how brain states and behaviors are generated by neural circuits, it would be useful to be able to perturb precisely the activity of specific cell types and pathways in the nonhuman primate nervous system. We used lentivirus to target the light-activated cation channel channelrhodopsin-2 (ChR2) specifically to excitatory neurons of the macaque frontal cortex. Using a laser-coupled optical fiber in conjunction with a recording microelectrode, we showed that activation of excitatory neurons resulted in well-timed excitatory and suppressive influences on neocortical neural networks.

Prosthetic systems for therapeutic optical activation and silencing of genetically-targeted neurons.

Many neural disorders are associated with aberrant activity in specific cell types or neural projection pathways embedded within the densely-wired, heterogeneous matter of the brain. An ideal therapy would permit correction of activity just in specific target neurons, while leaving other neurons unaltered. Recently our lab revealed that the naturally-occurring light-activated proteins channelrhodopsin-2 (ChR2) and halorhodopsin (Halo/NpHR) can, when genetically expressed in neurons, enable them to be safely, precisely, and reversibly activated and silenced by pulses of blue and yellow light, respectively.