Brain-wide coordination of decision formation and commitment.

Neural correlates of a subject's upcoming choice in decision making tasks are remarkably widespread throughout the brain, but how these brain-wide signals are coordinated remains unknown. Do brain regions reflect competing or shared decision computations? Are decision signals generated by distributed circuits or are they computed locally and then broadcast broadly? To address these fundamental questions, we took a brain-wide approach, simultaneously recording from thousands of neurons across up to twenty brain regions in rats performing a decision making task requiring gradual accumulation of auditory evidence. This allowed decoding, on single trials and for each of the simultaneously recorded regions, the time-varying state of the decision as it is being formed.

SLAy-ing oversplitting errors in high-density electrophysiology spike sorting.

The growing channel count of silicon probes has substantially increased the number of neurons recorded in electrophysiology (ephys) experiments, rendering traditional manual spike sorting impractical. Instead, modern ephys recordings are processed with automated methods that use waveform template matching to isolate putative single neurons. While scalable, automated methods are subject to assumptions that often fail to account for biophysical changes in action potential waveforms, leading to systematic errors.

Sleep need-dependent plasticity of a thalamic circuit promotes homeostatic recovery sleep.

Prolonged wakefulness leads to persistent, deep recovery sleep (RS). However, the neuronal circuits that mediate this process remain elusive. From a circuit screen in mice, we identified a group of thalamic nucleus reuniens (RE) neurons activated during sleep deprivation (SD) and required for sleep homeostasis.

Neuropixels Opto: Combining high-resolution electrophysiology and optogenetics.

High-resolution extracellular electrophysiology is the gold standard for recording spikes from distributed neural populations, and is especially powerful when combined with optogenetics for manipulation of specific cell types with high temporal resolution. We integrated these approaches into prototype Neuropixels Opto probes, which combine electronic and photonic circuits. These devices pack 960 electrical recording sites and two sets of 14 light emitters onto a 1 cm shank, allowing spatially addressable optogenetic stimulation with blue and red light.

Multi-day neuron tracking in high-density electrophysiology recordings using earth mover's distance.

Accurate tracking of the same neurons across multiple days is crucial for studying changes in neuronal activity during learning and adaptation. Advances in high-density extracellular electrophysiology recording probes, such as Neuropixels, provide a promising avenue to accomplish this goal. Identifying the same neurons in multiple recordings is, however, complicated by non-rigid movement of the tissue relative to the recording sites (drift) and loss of signal from some neurons.

Multi-day Neuron Tracking in High Density Electrophysiology Recordings using EMD.

Accurate tracking of the same neurons across multiple days is crucial for studying changes in neuronal activity during learning and adaptation. Advances in high density extracellular electrophysiology recording probes, such as Neuropixels, provide a promising avenue to accomplish this goal. Identifying the same neurons in multiple recordings is, however, complicated by non-rigid movement of the tissue relative to the recording sites (drift) and loss of signal from some neurons.

Volitional activation of remote place representations with a hippocampal brain-machine interface.

The hippocampus is critical for recollecting and imagining experiences. This is believed to involve voluntarily drawing from hippocampal memory representations of people, events, and places, including maplike representations of familiar environments. However, whether representations in such "cognitive maps" can be volitionally accessed is unknown.

Ultra-high density electrodes improve detection, yield, and cell type identification in neuronal recordings.

To understand the neural basis of behavior, it is essential to sensitively and accurately measure neural activity at single neuron and single spike resolution. Extracellular electrophysiology delivers this, but it has biases in the neurons it detects and it imperfectly resolves their action potentials. To minimize these limitations, we developed a silicon probe with much smaller and denser recording sites than previous designs, called Neuropixels Ultra ().

Robotic multi-probe single-actuator inchworm neural microdrive.

A wide range of techniques in neuroscience involve placing individual probes at precise locations in the brain. However, large-scale measurement and manipulation of the brain using such methods have been severely limited by the inability to miniaturize systems for probe positioning. Here, we present a fundamentally new, remote-controlled micropositioning approach composed of novel phase-change material-filled resistive heater micro-grippers arranged in an inchworm motor configuration.

Electrode pooling can boost the yield of extracellular recordings with switchable silicon probes.

State-of-the-art silicon probes for electrical recording from neurons have thousands of recording sites. However, due to volume limitations there are typically many fewer wires carrying signals off the probe, which restricts the number of channels that can be recorded simultaneously. To overcome this fundamental constraint, we propose a method called electrode pooling that uses a single wire to serve many recording sites through a set of controllable switches.

Neuropixels 2.0: A miniaturized high-density probe for stable, long-term brain recordings.

Measuring the dynamics of neural processing across time scales requires following the spiking of thousands of individual neurons over milliseconds and months. To address this need, we introduce the Neuropixels 2.0 probe together with newly designed analysis algorithms.

Neuropixels Data-Acquisition System: A Scalable Platform for Parallel Recording of 10 000+ Electrophysiological Signals.

Although CMOS fabrication has enabled a quick evolution in the design of high-density neural probes and neural-recording chips, the scaling and miniaturization of the complete data-acquisition systems has happened at a slower pace. This is mainly due to the complexity and the many requirements that change depending on the specific experimental settings. In essence, the fundamental challenge of a neural-recording system is getting the signals describing the largest possible set of neurons out of the brain and down to data storage for analysis.

Can One Concurrently Record Electrical Spikes from Every Neuron in a Mammalian Brain?

The classic approach to measure the spiking response of neurons involves the use of metal electrodes to record extracellular potentials. Starting over 60 years ago with a single recording site, this technology now extends to ever larger numbers and densities of sites. We argue, based on the mechanical and electrical properties of existing materials, estimates of signal-to-noise ratios, assumptions regarding extracellular space in the brain, and estimates of heat generation by the electronic interface, that it should be possible to fabricate rigid electrodes to concurrently record from essentially every neuron in the cortical mantle.

Multimodal in vivo brain electrophysiology with integrated glass microelectrodes.

Electrophysiology is the most used approach for the collection of functional data in basic and translational neuroscience, but it is typically limited to either intracellular or extracellular recordings. The integration of multiple physiological modalities for the routine acquisition of multimodal data with microelectrodes could be useful for biomedical applications, yet this has been challenging owing to incompatibilities of fabrication methods. Here, we present a suite of glass pipettes with integrated microelectrodes for the simultaneous acquisition of multimodal intracellular and extracellular information in vivo, electrochemistry assessments, and optogenetic perturbations of neural activity.

Evaluating the potential of using quantum dots for monitoring electrical signals in neurons.

Success in the projects aimed at providing an advanced understanding of the brain is directly predicated on making critical advances in nanotechnology. This Perspective addresses the unique interface of neuroscience and nanomaterials by considering the foundational problem of sensing neuron membrane voltage and offers a potential solution that may be facilitated by a prototypical nanomaterial. Despite substantial improvements, the visualization of instantaneous voltage changes within individual neurons, whether in cell culture or in vivo, at both the single-cell and network level at high speed remains complex and problematic.

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.

Large-scale, high-density (up to 512 channels) recording of local circuits in behaving animals.

Monitoring representative fractions of neurons from multiple brain circuits in behaving animals is necessary for understanding neuronal computation. Here, we describe a system that allows high-channel-count recordings from a small volume of neuronal tissue using a lightweight signal multiplexing headstage that permits free behavior of small rodents. The system integrates multishank, high-density recording silicon probes, ultraflexible interconnects, and a miniaturized microdrive.

Thalamocortical input onto layer 5 pyramidal neurons measured using quantitative large-scale array tomography.

The subcellular locations of synapses on pyramidal neurons strongly influences dendritic integration and synaptic plasticity. Despite this, there is little quantitative data on spatial distributions of specific types of synaptic input. Here we use array tomography (AT), a high-resolution optical microscopy method, to examine thalamocortical (TC) input onto layer 5 pyramidal neurons.

Excitation spectra and brightness optimization of two-photon excited probes.

Two-photon probe excitation data are commonly presented as absorption cross section or molecular brightness (the detected fluorescence rate per molecule). We report two-photon molecular brightness spectra for a diverse set of organic and genetically encoded probes with an automated spectroscopic system based on fluorescence correlation spectroscopy. The two-photon action cross section can be extracted from molecular brightness measurements at low excitation intensities, while peak molecular brightness (the maximum molecular brightness with increasing excitation intensity) is measured at higher intensities at which probe photophysical effects become significant.

Single-molecule DNA sequencing of a viral genome.

The full promise of human genomics will be realized only when the genomes of thousands of individuals can be sequenced for comparative analysis. A reference sequence enables the use of short read length. We report an amplification-free method for determining the nucleotide sequence of more than 280,000 individual DNA molecules simultaneously.