Multi-shank 1024 channels active SiNAPS probe for large multi-regional topographical electrophysiological mapping of neural dynamics.

Implantable active dense CMOS neural probes unlock the possibility of spatiotemporally resolving the activity of hundreds of single neurons in multiple brain circuits to investigate brain dynamics. Mapping neural dynamics in brain circuits with anatomical structures spanning several millimeters, however, remains challenging. Here, we demonstrate the first CMOS neural probe for mapping intracortical neural dynamics (both LFPs and spikes) in awake, behaving mice from an area >4 mm.

Construction of ThermoMaze.

Physiological changes during awake immobility-related brain states remain one of the great unexplored behavioral states. Controlling periods of awake immobility is challenging because restraining the animal is stressful and is accompanied by altered physiological states. Here, we describe the ThermoMaze, a behavioral paradigm that allows for the collection of large amounts of physiological data while the animal rests at distinct experimenter-determined locations.

Self-Assembled Origami Neural Probes for Scalable, Multifunctional, Three-Dimensional Neural Interface.

Flexible intracortical neural probes have drawn attention for their enhanced longevity in high-resolution neural recordings due to reduced tissue reaction. However, the conventional monolithic fabrication approach has met significant challenges in: (i) scaling the number of recording sites for electrophysiology; (ii) integrating of other physiological sensing and modulation; and (iii) configuring into three-dimensional (3D) shapes for multi-sided electrode arrays. We report an innovative self-assembly technology that allows for implementing flexible origami neural probes as an effective alternative to overcome these challenges.

Transcranial electric stimulation modulates firing rate at clinically relevant intensities.

Background: Notwithstanding advances with low-intensity transcranial electrical stimulation (tES), there remain questions about the efficacy of clinically realistic electric fields on neuronal function.

Objective: To measure electric fields magnitude and their effects on neuronal firing rate of hippocampal neurons in freely moving rats, and to establish calibrated computational models of current flow.

Methods: Current flow models were calibrated on electric field measures in the motor cortex (n = 2 anesthetized rats) and hippocampus.

Interaction of acetylcholine and oxytocin neuromodulation in the hippocampus.

A postulated role of subcortical neuromodulators is to control brain states. Mechanisms by which different neuromodulators compete or cooperate at various temporal scales remain an open question. We investigated the interaction of acetylcholine (ACh) and oxytocin (OXT) at slow and fast timescales during various brain states.

Transcranial electric stimulation modulates firing rate at clinically relevant intensities.

Notwithstanding advances with low-intensity transcranial electrical stimulation (TES), there remain questions about the efficacy of clinically realistic electric fields on neuronal function. We used Neuropixels 2.0 probe with 384 channels in an in-vivo rat model of TES to detect effects of weak fields on neuronal firing rate.

Brain-implanted conductors amplify radiofrequency fields in rodents: Advantages and risks.

Over the past few decades, daily exposure to radiofrequency (RF) fields has been increasing due to the rapid development of wireless and medical imaging technologies. Under extreme circumstances, exposure to very strong RF energy can lead to heating of body tissue, even resulting in tissue injury. The presence of implanted devices, moreover, can amplify RF effects on surrounding tissue.

Autonomous animal heating and cooling system for temperature-regulated magnetic resonance experiments.

Temperature is a hallmark parameter influencing almost all magnetic resonance properties (e.g., T , T , proton density, and diffusion).

Simultaneous electrophysiology and optogenetic perturbation of the same neurons in chronically implanted animals using μLED silicon probes.

Micro-light-emitting-diode (μLED) silicon probes feature independently controllable miniature light-emitting-diodes (LEDs) embedded at several positions in each shank of a multi-shank probe, enabling temporally and spatially precise optogenetic neural circuit interrogation. Here, we present a protocol for performing causal and reproducible neural circuit manipulations in chronically implanted, freely moving animals. We describe steps for introducing optogenetic constructs, preparing and implanting a μLED probe, performing simultaneous in vivo electrophysiology with focal optogenetic perturbation, and recovering a probe following termination of an experiment.

ThermoMaze: A behavioral paradigm for readout of immobility-related brain events.

Brain states fluctuate between exploratory and consummatory phases of behavior. These state changes affect both internal computation and the organism's responses to sensory inputs. Understanding neuronal mechanisms supporting exploratory and consummatory states and their switching requires experimental control of behavioral shifts and collecting sufficient amounts of brain data.

Autonomous animal heating and cooling system for temperature-regulated MR experiments.

Temperature is a hallmark parameter influencing almost all magnetic resonance properties (e.g., T\textsubscript{1}, T\textsubscript{2}, proton density, diffusion and more).

Brain rhythms have come of age.

Neuronal oscillations offer access to neuronal operations, bringing microscopic and macroscopic mechanisms, experimental methods, and explanations to a common platform. The field of brain rhythms has become the agora of discussions from temporal coordination of neuronal populations within and across brain regions to cognitive phenomena, including language and brain diseases.

Multilayer Arrays for Neurotechnology Applications (MANTA): Chronically Stable Thin-Film Intracortical Implants.

Flexible implantable neurointerfaces show great promise in addressing one of the major challenges of implantable neurotechnology, namely the loss of signal connected to unfavorable probe tissue interaction. The authors here show how multilayer polyimide probes allow high-density intracortical recordings to be combined with a reliable long-term stable tissue interface, thereby progressing toward chronic stability of implantable neurotechnology. The probes could record 10-60 single units over 5 months with a consistent peak-to-peak voltage at dimensions that ensure robust handling and insulation longevity.

Simultaneous Electrophysiology and Optogenetic Perturbation of the Same Neurons in Chronically Implanted Animals using μLED Silicon Probes.

Unlabelled: Optogenetics are a powerful tool for testing how a neural circuit influences neural activity, cognition, and behavior. Accordingly, the number of studies employing optogenetic perturbation has grown exponentially over the last decade. However, recent studies have highlighted that the impact of optogenetic stimulation/silencing can vary depending on the construct used, the local microcircuit connectivity, extent/power of illumination, and neuron types perturbed.

HectoSTAR μLED Optoelectrodes for Large-Scale, High-Precision In Vivo Opto-Electrophysiology.

Dynamic interactions within and across brain areas underlie behavioral and cognitive functions. To understand the basis of these processes, the activities of distributed local circuits inside the brain of a behaving animal must be synchronously recorded while the inputs to these circuits are precisely manipulated. Even though recent technological advances have enabled such large-scale recording capabilities, the development of the high-spatiotemporal-resolution and large-scale modulation techniques to accompany those recordings has lagged.

Brain temperature affects quantitative features of hippocampal sharp wave ripples.

Biochemical mechanisms are temperature dependent. Brain temperature shows wide variations across brain states, and such changes may explain quantitative changes in network oscillations. Here, we report on the relationship between various hippocampal sharp wave ripple features to brain temperature.

A 3.1-5.2GHz, Energy-Efficient Single Antenna, Cancellation-Free, Bitwise Time-Division Duplex Transceiver for High Channel Count Optogenetic Neural Interface.

We report an energy-efficient, cancellation-free, bit-wise time-division duplex (B-TDD) transceiver (TRX) for real-time closed-loop control of high channel count neural interfaces. The proposed B-TDD architecture consists of a duty-cycled ultra-wide band (UWB) transmitter (3.1-5 GHz) and a switching U-NII band (5.

Neuronal activity under transcranial radio-frequency stimulation in metal-free rodent brains in-vivo.

As the use of Radio Frequency (RF) technologies increases, the impact of RF radiation on neurological function continues to receive attention. Whether RF radiation can modulate ongoing neuronal activity by non-thermal mechanisms has been debated for decades. However, the interactions between radiated energy and metal-based neural probes during experimentation could impact neural activity, making interpretation of the results difficult.

3D-printed Recoverable Microdrive and Base Plate System for Rodent Electrophysiology.

Extracellular recordings in freely moving animals allow the monitoring of brain activity from populations of neurons at single-spike temporal resolution. While state-of-the-art electrophysiological recording devices have been developed in recent years (, µLED and Neuropixels silicon probes), implantation methods for silicon probes in rats and mice have not advanced substantially for a decade. The surgery is complex, takes time to master, and involves handling expensive devices and valuable animal subjects.

A Miniaturized 256-Channel Neural Recording Interface With Area-Efficient Hybrid Integration of Flexible Probes and CMOS Integrated Circuits.

We report a miniaturized, minimally invasive high-density neural recording interface that occupies only a 1.53 mm footprint for hybrid integration of a flexible probe and a 256-channel integrated circuit chip. To achieve such a compact form factor, we developed a custom flip-chip bonding technique using anisotropic conductive film and analog circuit-under-pad in a tiny pitch of 75 μm.

Metal microdrive and head cap system for silicon probe recovery in freely moving rodent.

High-yield electrophysiological extracellular recording in freely moving rodents provides a unique window into the temporal dynamics of neural circuits. Recording from unrestrained animals is critical to investigate brain activity during natural behaviors. The use and implantation of high-channel-count silicon probes represent the largest cost and experimental complexity associated with such recordings making a recoverable and reusable system desirable.

Novel diamond shuttle to deliver flexible neural probe with reduced tissue compression.

The ability to deliver flexible biosensors through the toughest membranes of the central and peripheral nervous system is an important challenge in neuroscience and neural engineering. Bioelectronic devices implanted through dura mater and thick epineurium would ideally create minimal compression and acute damage as they reach the neurons of interest. We demonstrate that a three-dimensional diamond shuttle can be easily made with a vertical support to deliver ultra-compliant polymer microelectrodes (4.

Artifact-free and high-temporal-resolution in vivo opto-electrophysiology with microLED optoelectrodes.

The combination of in vivo extracellular recording and genetic-engineering-assisted optical stimulation is a powerful tool for the study of neuronal circuits. Precise analysis of complex neural circuits requires high-density integration of multiple cellular-size light sources and recording electrodes. However, high-density integration inevitably introduces stimulation artifact.

Dual color optogenetic control of neural populations using low-noise, multishank optoelectrodes.

Optogenetics allows for optical manipulation of neuronal activity and has been increasingly combined with intra- and extra-cellular electrophysiological recordings. Genetically-identified classes of neurons are optically manipulated, though the versatility of optogenetics would be increased if independent control of distinct neural populations could be achieved on a sufficient spatial and temporal resolution. We report a scalable multi-site optoelectrode design that allows simultaneous optogenetic control of two spatially intermingled neuronal populations .