Fully integrated silicon probes for high-density recording of neural activity.

Sensory, motor and cognitive operations involve the coordinated action of large neuronal populations across multiple brain regions in both superficial and deep structures. Existing extracellular probes record neural activity with excellent spatial and temporal (sub-millisecond) resolution, but from only a few dozen neurons per shank. Optical Ca imaging offers more coverage but lacks the temporal resolution needed to distinguish individual spikes reliably and does not measure local field potentials.

Spatial Organization of Chromatic Pathways in the Mouse Dorsal Lateral Geniculate Nucleus.

Unlabelled: In both dichromats and trichromats, cone opsin signals are maintained independently in cones and combined at the bipolar and retinal ganglion cell level, creating parallel color opponent pathways to the central visual system. Like other dichromats, the mouse retina expresses a short-wavelength (S) and a medium-wavelength (M) opsin, with the S-opsin shifted to peak sensitivity in the ultraviolet (UV) range. Unlike in primates, nonuniform opsin expression across the retina and coexpression in single cones creates a mostly mixed chromatic signal.

Optogenetics in Mice Performing a Visual Discrimination Task: Measurement and Suppression of Retinal Activation and the Resulting Behavioral Artifact.

Optogenetic techniques are used widely to perturb and interrogate neural circuits in behaving animals, but illumination can have additional effects, such as the activation of endogenous opsins in the retina. We found that illumination, delivered deep into the brain via an optical fiber, evoked a behavioral artifact in mice performing a visually guided discrimination task. Compared with blue (473 nm) and yellow (589 nm) illumination, red (640 nm) illumination evoked a greater behavioral artifact and more activity in the retina, the latter measured with electrical recordings.

Neurodata Without Borders: Creating a Common Data Format for Neurophysiology.

The Neurodata Without Borders (NWB) initiative promotes data standardization in neuroscience to increase research reproducibility and opportunities. In the first NWB pilot project, neurophysiologists and software developers produced a common data format for recordings and metadata of cellular electrophysiology and optical imaging experiments. The format specification, application programming interfaces, and sample datasets have been released.

Identifying robust communities and multi-community nodes by combining top-down and bottom-up approaches to clustering.

Biological functions are carried out by groups of interacting molecules, cells or tissues, known as communities. Membership in these communities may overlap when biological components are involved in multiple functions. However, traditional clustering methods detect non-overlapping communities.

Closed-loop, ultraprecise, automated craniotomies.

A large array of neuroscientific techniques, including in vivo electrophysiology, two-photon imaging, optogenetics, lesions, and microdialysis, require access to the brain through the skull. Ideally, the necessary craniotomies could be performed in a repeatable and automated fashion, without damaging the underlying brain tissue. Here we report that when drilling through the skull a stereotypical increase in conductance can be observed when the drill bit passes through the skull base.

High-density optrodes for multi-scale electrophysiology and optogenetic stimulation.

We demonstrate the design and implementation of hybrid optical-electrical probes (`optrodes') for high resolution electrophysiology and optogenetic stimulation of neurons in multiple brain areas. Our 64-channel implantable optrodes are minimally invasive (50 μm × 20 μm) and span 1~2 mm. To minimize tethering forces on the brain tissue a monolithic high-density flexible cable (6 μm thin) connects the probe to a lightweight headstage (1.

Construction of direction selectivity through local energy computations in primary visual cortex.

Despite detailed knowledge about the anatomy and physiology of neurons in primary visual cortex (V1), the large numbers of inputs onto a given V1 neuron make it difficult to relate them to the neuron's functional properties. For example, models of direction selectivity (DS), such as the Energy Model, can successfully describe the computation of phase-invariant DS at a conceptual level, while leaving it unclear how such computations are implemented by cortical circuits. Here, we use statistical modeling to derive a description of DS computation for both simple and complex cells, based on physiologically plausible operations on their inputs.

Functional connectivity and tuning curves in populations of simultaneously recorded neurons.

How interactions between neurons relate to tuned neural responses is a longstanding question in systems neuroscience. Here we use statistical modeling and simultaneous multi-electrode recordings to explore the relationship between these interactions and tuning curves in six different brain areas. We find that, in most cases, functional interactions between neurons provide an explanation of spiking that complements and, in some cases, surpasses the influence of canonical tuning curves.

Multiplexed, high density electrophysiology with nanofabricated neural probes.

Extracellular electrode arrays can reveal the neuronal network correlates of behavior with single-cell, single-spike, and sub-millisecond resolution. However, implantable electrodes are inherently invasive, and efforts to scale up the number and density of recording sites must compromise on device size in order to connect the electrodes. Here, we report on silicon-based neural probes employing nanofabricated, high-density electrical leads.

Nyquist interpolation improves neuron yield in multiunit recordings.

Multiunit electrodes, in particular tetrodes and polytrodes, are able to isolate action potentials from many neurons simultaneously. However, inaccuracies in the post-acquisition reconstruction of recorded spike waveforms can affect the reliability of spike detection and sorting. Here we show that bandlimited interpolation with sample-and-hold delay correction reduces waveform variability, leading to improved reliability of threshold-based event detection and improved spike sorting accuracy.

Polytrodes: high-density silicon electrode arrays for large-scale multiunit recording.

We developed a variety of 54-channel high-density silicon electrode arrays (polytrodes) designed to record from large numbers of neurons spanning millimeters of brain. In cat visual cortex, it was possible to make simultaneous recordings from >100 well-isolated neurons. Using standard clustering methods, polytrodes provide a quality of single-unit isolation that surpasses that attainable with tetrodes.

Loss of reflex inhibition following muscle tendon stimulation in essential tremor.

Electrical stimulation of human upper limb muscle tendons produces a reflex inhibition (I(1)) in the same muscles. This inhibition is reduced in Parkinson's disease (PD), prompting a similar study of essential tremor (ET). In essential tremor, two of eight subjects had no discernible inhibition, even following supramaximal stimulation (< 80 mA) of the tendons from extensor digitorum communis and extensor pollicis brevis.