Jakob Voigts

Unsupervised Whisker Tracking in Unrestrained Behaving Animals

Understanding how whisker-based tactile information is represented in the nervous system requires quantification of sensory input and observation of neural activity during whisking and whisker touch. Chronic electrophysiological methods have long been available to study neural responses in awake and behaving animals; however, methods to quantify the sensory input on whiskers have not yet been developed. Here we describe an unsupervised algorithm to track whisker movements in high-speed video recordings and to quantify the statistics of the tactile information on whiskers in freely behaving animals during haptic object exploration. The algorithm does not require human identification of whiskers, nor does it assume the shape, location, orientation, length of whiskers, or direction of the whisker movements. The algorithm performs well on temporary loss of whisker visibility and under low-light/low-contrast conditions even with inherent anisotropic noise and non-Gaussian variability in the signal. Using this algorithm, we define the speed [protraction (P), 1,081 +/- 322; retraction (R), 1,564 +/- 549 degrees /s], duration (P, 34 +/- 10; R, 24 +/- 8 ms), amplitude (P = R, 40 +/- 13 degrees ), and frequency (19 +/- 7 Hz) of active whisking in freely behaving mice. We furthermore quantify whisker deflection induced changes in whisking kinematics and calculate the statistics (i.e., speed, amplitude and duration) of whisker touch and finally show that whisker deprivation does not alter whisking kinematics during haptic exploration.

Thalamic reticular nucleus induces fast and local modulation of arousal state

During low arousal states such as drowsiness and sleep, cortical neurons exhibit rhythmic slow wave activity associated with periods of neuronal silence. Slow waves are locally regulated, and local slow wave dynamics are important for memory, cognition, and behaviour. While several brainstem structures for controlling global sleep states have now been well characterized, a mechanism underlying fast and local modulation of cortical slow waves has not been identified. Here, using optogenetics and whole cortex electrophysiology, we show that local tonic activation of thalamic reticular nucleus (TRN) rapidly induces slow wave activity in a spatially restricted region of cortex. These slow waves resemble those seen in sleep, as cortical units undergo periods of silence phase-locked to the slow wave. Furthermore, animals exhibit behavioural changes consistent with a decrease in arousal state during TRN stimulation. We conclude that TRN can induce rapid modulation of local cortical state. DOI: http://dx.doi.org/10.7554/eLife.08760.001

Tactile object localization by anticipatory whisker motion

Rodents use rhythmic protractions of their whiskers to locate objects in space. The amplitude of these protractions is reduced when whiskers contact objects, leading to a tendency of whiskers to only lightly touch the environment. While the impact of this process on the sensory input has been studied, little is known about how sensory input causes this change in the motor pattern. Here, using high-speed imaging of whisking in mice, we simultaneously measured whisker contacts and the resulting whisking motion. We found that mice precisely target their whisker protractions to the distance at which they expect objects. This modulation does not depend on the current sensory input and remains stable for at least one whisking cycle when there is no object contact or when the object position is changed. As a result, the timing and other information carried by whisker contacts encodes how well each protraction was matched to the object, functioning as an error signal. Whisker contacts can thus encode a mismatch between expected object locations and the actual environment.

Design and fabrication of ultralight weight, adjustable multi-electrode probes for electrophysiological recordings in mice.

The number of physiological investigations in the mouse, mus musculus, has experienced a recent surge, paralleling the growth in methods of genetic targeting for microcircuit dissection and disease modeling. The introduction of optogenetics, for example, has allowed for bidirectional manipulation of genetically-identified neurons, at an unprecedented temporal resolution. To capitalize on these tools and gain insight into dynamic interactions among brain microcircuits, it is essential that one has the ability to record from ensembles of neurons deep within the brain of this small rodent, in both head-fixed and freely behaving preparations. To record from deep structures and distinct cell layers requires a preparation that allows precise advancement of electrodes towards desired brain regions. To record neural ensembles, it is necessary that each electrode be independently movable, allowing the experimenter to resolve individual cells while leaving neighboring electrodes undisturbed. To do both in a freely behaving mouse requires an electrode drive that is lightweight, resilient, and highly customizable for targeting specific brain structures. A technique for designing and fabricating miniature, ultralight weight, microdrive electrode arrays that are individually customizable and easily assembled from commercially available parts is presented. These devices are easily scalable and can be customized to the structure being targeted; it has been used successfully to record from thalamic and cortical regions in a freely behaving animal during natural behavior.

Open Ephys electroencephalography (Open Ephys + EEG): a modular, low-cost, open-source solution to human neural recording

OBJECTIVE Electroencephalography (EEG) offers a unique opportunity to study human neural activity non-invasively with millisecond resolution using minimal equipment in or outside of a lab setting. EEG can be combined with a number of techniques for closed-loop experiments, where external devices are driven by specific neural signals. However, reliable, commercially available EEG systems are expensive, often making them impractical for individual use and research development. Moreover, by design, a majority of these systems cannot be easily altered to the specification needed by the end user. We focused on mitigating these issues by implementing open-source tools to develop a new EEG platform to drive down research costs and promote collaboration and innovation. APPROACH Here, we present methods to expand the open-source electrophysiology system, Open Ephys (www.openephys.org), to include human EEG recordings. We describe the equipment and protocol necessary to interface various EEG caps with the Open Ephys acquisition board, and detail methods for processing data. We present applications of Open Ephys  +  EEG as a research tool and discuss how this innovative EEG technology lays a framework for improved closed-loop paradigms and novel brain-computer interface experiments. MAIN RESULTS The Open Ephys  +  EEG system can record reliable human EEG data, as well as human EMG data. A side-by-side comparison of eyes closed 8-14 Hz activity between the Open Ephys  +  EEG system and the Brainvision ActiCHamp EEG system showed similar average power and signal to noise. SIGNIFICANCE Open Ephys  +  EEG enables users to acquire high-quality human EEG data comparable to that of commercially available systems, while maintaining the price point and extensibility inherent to open-source systems.

An animal-actuated rotational head-fixation system for 2-photon imaging during 2-d navigation

Understanding how the biology of the brain gives rise to the computations that drive behavior requires high fidelity, large scale, and subcellular measurements of neural activity. 2-photon microscopy is the primary tool that satisfies these requirements, particularly for measurements during behavior. However, this technique requires rigid head-fixation, constraining the behavioral repertoire of experimental subjects. Increasingly, complex task paradigms are being used to investigate the neural substrates of complex behaviors, including navigation of complex environments, resolving uncertainty between multiple outcomes, integrating unreliable information over time, and/or building internal models of the world. In rodents, planning and decision making processes are often expressed via head and body motion. This produces a significant limitation for head-fixed two-photon imaging. We therefore developed a system that overcomes a major problem of head-fixation: the lack of rotational vestibular input. The system measures rotational strain exerted by mice on the head restraint, which consequently drives a motor, rotating the constraint system and dissipating the strain. This permits mice to rotate their heads in the azimuthal plane with negligible inertia and friction. This stable rotating head-fixation system allows mice to explore physical or virtual 2-D environments. To demonstrate the performance of our system, we conducted 2-photon GCaMP6f imaging in somas and dendrites of pyramidal neurons in mouse retrosplenial cortex. We show that the subcellular resolution of the system’s 2-photon imaging is comparable to that of conventional head-fixed experiments. Additionally, this system allows the attachment of heavy instrumentation to the animal, making it possible to extend the approach to large-scale electrophysiology experiments in the future. Our method enables the use of state-of-the-art imaging techniques while animals perform more complex and naturalistic behaviors than currently possible, with broad potential applications in systems neuroscience.