A claustrum in reptiles and its role in slow-wave sleep

The mammalian claustrum, owing to its widespread connectivity with other forebrain structures, has been hypothesized to mediate functions that range from decision-making to consciousness(1). Here we report that a homologue of the claustrum, identified by single-cell transcriptomics and viral tracing of connectivity, also exists in a reptile-the Australian bearded dragon Pogona vitticeps. In Pogona, the claustrum underlies the generation of sharp waves during slow-wave sleep. The sharp waves, together with superimposed high-frequency ripples(2), propagate to the entire neighbouring pallial dorsal ventricular ridge (DVR). Unilateral or bilateral lesions of the claustrum suppress the production of sharp-wave ripples during slow-wave sleep in a unilateral or bilateral manner, respectively, but do not affect the regular and rapidly alternating sleep rhythm that is characteristic of sleep in this species(3). The claustrum is thus not involved in the generation of the sleep rhythm itself. Tract tracing revealed that the reptilian claustrum projects widely to a variety of forebrain areas, including the cortex, and that it receives converging inputs from, among others, areas of the mid- and hindbrain that are known to be involved in wake-sleep control in mammals(4-6). Periodically modulating the concentration of serotonin in the claustrum, for example, caused a matching modulation of sharp-wave production there and in the neighbouring DVR. Using transcriptomic approaches, we also identified a claustrum in the turtle Trachemys scripta, a distant reptilian relative of lizards. The claustrum is therefore an ancient structure that was probably already present in the brain of the common vertebrate ancestor of reptiles and mammals. It may have an important role in the control of brain states owing to the ascending input it receives from the mid- and hindbrain, its widespread projections to the forebrain and its role in sharp-wave generation during slow-wave sleep

Nat Methods

Advances in techniques for recording large-scale brain activity contribute to both the elucidation of neurophysiological principles and the development of brain-machine interfaces (BMIs). Here we describe a neurophysiological paradigm for performing tethered and wireless large-scale recordings based on movable volumetric three-dimensional (3D) multielectrode implants. This approach allowed us to isolate up to 1,800 neurons (units) per animal and simultaneously record the extracellular activity of close to 500 cortical neurons, distributed across multiple cortical areas, in freely behaving rhesus monkeys. The method is expandable, in principle, to thousands of simultaneously recorded channels. It also allows increased recording longevity (5 consecutive years) and recording of a broad range of behaviors, such as social interactions, and BMI paradigms in freely moving primates. We propose that wireless large-scale recordings could have a profound impact on basic primate neurophysiology research while providing a framework for the development and testing of clinically relevant neuroprostheses.20142014-12-01T00:00:00ZT32 GM008441/GM/NIGMS NIH HHS/United StatesDP1MH099903/DP/NCCDPHP CDC HHS/United StatesR01NS073952/NS/NINDS NIH HHS/United StatesDP1 MH099903/MH/NIMH NIH HHS/United StatesUL1 TR001117/TR/NCATS NIH HHS/United StatesR01 NS073952/NS/NINDS NIH HHS/United StatesDP1 OD006798/OD/NIH HHS/United States24776634PMC416103

A modular multi electrode array system for electrogenic cell characterisation and cardiotoxicity applications

Multi electrode array (MEA) systems have evolved from custom-made experimental tools, exploited for neural research, into commercially available systems that are used throughout non-invasive electrophysiological study. MEA systems are used in conjunction with cells and tissues from a number of differing organisms (e.g. mice, monkeys, chickens, plants). The development of MEA systems has been incremental over the past 30 years due to constantly changing specific bioscientific requirements in research. As the application of MEA systems continues to diversify contemporary commercial systems are requiring increased levels of sophistication and greater throughput capabilities. [Continues.

Enhanced recording paradigms and advanced analyses of peripheral nerve fibers SPiike software

[eng] The aim of this work is to investigate the human nociceptive system at the peripheral level. Researchers are still debating how the pain perception arises from this very intricate network. The human perception is the most elusive part of our knowledge since different subsystems are involved. The external information such as noxious stimuli must be processed at the peripheral level and through signal cascades and transduction this signal must reach the brain. At the brain level the information is processed and some decisions are taken, such as the well-known fight-or-flight response. In the introduction, the author describes how the human nociceptive system works and in which way the noxious stimulus is converted into a signal understandable by the brain. Several cortical and subcortical areas are involved in this signal processing and going deeper in this assembly line the information becomes more abstracted. The whole pathway is fundamental for pain perception, however some diseases start at the peripheral level. This in turn makes wrong signals reaching the brain. The brain is then processing information that are not real and the responses do not suit with the needs. Therefore, the peripheral system must be investigated and understood firstly, since some central diseases may have a peripheral component as well. With this purpose in mind the microneurography technique has been used. This technique has got some complexity and a computer-aided system must be implemented. The hardware aims to filter out the noisy signal and perform recording and stimulation of the neural fibers. The software is instead used to make the stimulation and recording as automatic as possible in a way that researchers do not have to deal with a lot of parameters and steps to carry out this powerful but also time consuming technique. Some software are already available in the market however even if they work fine with slow conduction fibers such as C-fibers they cannot cope with faster neurons (e.g. Aδ fibers). The aim of this work is to create a software (i.e. SPiike) able to stimulate and record every type of fibers implementing advanced analysis technique as well. Furthermore, considering that some in vivo experiments have been pursued within the project to check the functionality of the software, more specifically in rats and mice, the comparison between human nociceptors and mouse nociceptors is depicted in this section. In the method section, the experimental approach is described step by step. This is composed by several systems that work together for the stimulation, recording and analysis of the neural fibers. The control and acquisition module is composed by the software and a data acquisition board that trigger the stimulator and record the filtered signal. The stimulation module is composed by a stimulator that can be tuned as wish through dedicated knobs. Then the stimulus is delivered to the animal model (or the human patient) and the signal is recorded though a microelectrode inserted into the sciatic nerve. The amplification module is filtering out the noisy signal and is feeding a audio monitor for helping the researcher during the insertion of the electrode inside the nerve and it provides support during the whole experiment giving insights on fiber discharges. In this section the whole setup is described in details as well as the devices needed for the recording. Furthermore, the software development that is the core of this project is described as well, with all the considerations that must be considered during coding. Indeed, the flow chart must be followed methodically in order to minimize bugs and errors that may arise in the final product. Thus a description of the compiler and the Matlab IDE is given along with system and software requirements for the making of the SPiike software. Eventually the explanation of embedded functionalities and capabilities of SPiike is depicted in the final part of this section. This software is indeed able to stimulate slow conducting fibers as well as faster ones, and enhanced analysis techniques such as supervised machine learning are implemented. In the results section, the graphical user interface of the Spiike software is reveled. It resembles the one of another software already available in the market, with a filtered signal and a raster plot embedded on it. However, this software is more user-friendly and it accounts with icons and drop-down menus that enhance the experience of the users during the use of the tool, making their interactions smooth and intuitive. The SPiike software is subdivide into two different tools, a recording module and a analysis module. The former allows the stimulation and recording of neural fibers with a stimulation frequency up to 1000Hz and some online analysis can be conducted to have insights on fibers type and behavior. The analysis module is instead a more powerful analysis environment that can retrieve the dataset recorded with the other module or with the LabChart software. Advanced analysis techniques are implemented in this module, this is meant to speed up fiber classification and analysis. Conclusion and discussion provide a overview on some results. These will be compared to those obtainable through other software available in the market. In this section, pros and cons of the new implemented software, SPiike, will be described as well

Wireless power and data transmission to high-performance implantable medical devices

Novel techniques for high-performance wireless power transmission and data interfacing with implantable medical devices (IMDs) were proposed. Several system- and circuit-level techniques were developed towards the design of a novel wireless data and power transmission link for a multi-channel inductively-powered wireless implantable neural-recording and stimulation system. Such wireless data and power transmission techniques have promising prospects for use in IMDs such as biosensors and neural recording/stimulation devices, neural interfacing experiments in enriched environments, radio-frequency identification (RFID), smartcards, near-field communication (NFC), wireless sensors, and charging mobile devices and electric vehicles. The contributions in wireless power transfer are the development of an RFID-based closed-loop power transmission system, a high-performance 3-coil link with optimal design procedure, circuit-based theoretical foundation for magnetic-resonance-based power transmission using multiple coils, a figure-of-merit for designing high-performance inductive links, a low-power and adaptive power management and data transceiver ASIC to be used as a general-purpose power module for wireless electrophysiology experiments, and a Q-modulated inductive link for automatic load matching. In wireless data transfer, the contributions are the development of a new modulation technique called pulse-delay modulation for low-power and wideband near-field data communication and a pulse-width-modulation impulse-radio ultra-wideband transceiver for low-power and wideband far-field data transmission.Ph.D

Closed-loop approaches for innovative neuroprostheses

The goal of this thesis is to study new ways to interact with the nervous system in case of damage or pathology. In particular, I focused my effort towards the development of innovative, closed-loop stimulation protocols in various scenarios: in vitro, ex vivo, in vivo

Developing neurostimulation techniques to investigate antidepressant and mood modulating behaviors / by Rajas Prakash Kale

 My PhD consisted of a multidisciplinary approach towards primary research in the field of translational neuroscience. Incorporation of preclinical research, behavioral neuroscience, translational psychiatry, neural engineering, and biomedical device development techniques drives my continuing passion towards helping patients through innovation

Neurophysiological mechanisms of sensorimotor recovery from stroke

Ischemic stroke often results in the devastating loss of nervous tissue in the cerebral cortex, leading to profound motor deficits when motor territory is lost, and ultimately resulting in a substantial reduction in quality of life for the stroke survivor. The International Classification of Functioning, Disability and Health (ICF) was developed in 2002 by the World Health Organization (WHO) and provides a framework for clinically defining impairment after stroke. While the reduction of burdens due to neurological disease is stated as a mission objective of the National Institute of Neurological Disorders and Stroke (NINDS), recent clinical trials have been unsuccessful in translating preclinical research breakthroughs into actionable therapeutic treatment strategies with meaningful progress towards this goal. This means that research expanding another NINDS mission is now more important than ever: improving fundamental knowledge about the brain and nervous system in order to illuminate the way forward. Past work in the monkey model of ischemic stroke has suggested there may be a relationship between motor improvements after injury and the ability of the animal to reintegrate sensory and motor information during behavior. This relationship may be subserved by sprouting cortical axonal processes that originate in the spared premotor cortex after motor cortical injury in squirrel monkeys. The axons were observed to grow for relatively long distances (millimeters), significantly changing direction so that it appears that they specifically navigate around the injury site and reorient toward the spared sensory cortex. Critically, it remains unknown whether such processes ever form functional synapses, and if they do, whether such synapses perform meaningful calculations or other functions during behavior. The intent of this dissertation was to study this phenomenon in both intact rats and rats with a focal ischemia in primary motor cortex (M1) contralateral to the preferred forelimb during a pellet retrieval task. As this proved to be a challenging and resource-intensive endeavor, a primary objective of the dissertation became to provide the tools to facilitate such a project to begin with. This includes the creation of software, hardware, and novel training and behavioral paradigms for the rat model. At the same time, analysis of previous experimental data suggested that plasticity in the neural activity of the bilateral motor cortices of rats performing pellet retrievals after focal M1 ischemia may exhibit its most salient changes with respect to functional changes in behavior via mechanisms that were different than initially hypothesized. Specifically, a major finding of this dissertation is the finding that evidence of plasticity in the unit activity of bilateral motor cortical areas of the reaching rat is much stronger at the level of population features. These features exhibit changes in dynamics that suggest a shift in network fixed points, which may relate to the stability of filtering performed during behavior. It is therefore predicted that in order to define recovery by comparison to restitution, a specific type of fixed point dynamics must be present in the cortical population state. A final suggestion is that the stability or presence of these dynamics is related to the reintegration of sensory information to the cortex, which may relate to the positive impact of physical therapy during rehabilitation in the postacute window. Although many more rats will be needed to state any of these findings as a definitive fact, this line of inquiry appears to be productive for identifying targets related to sensorimotor integration which may enhance the efficacy of future therapeutic strategies

Studies on the respiratory modulation of sympathetic activity

Sympathetic activity is modulated by central respiratory drive. Studies using whole nerve recordings in the rat have demonstrated different patterns of respiratory modulation in various sympathetic nerves. These regional differences in the discharge patterns of sympathetic outflows may result from either varying proportions of sympathetic neurones with a particular respiratory-related discharge pattern contributing to each whole-nerve activity or sympathetic preganglionic neurones (SPNs) projecting into different nerves having characteristic respiratory modulations. The present study has investigated the respiratory-related discharge patterns of a group of SPNs projecting to the lumbar sympathetic chain (LSC). Furthermore, the hypothesis that caudal raphe nuclei (raphe obscurus, pallidus and magnus) convey central respiratory drive onto sympathetic outflow has been examined. In anaesthetized and vagotomized rats extracellular recordings were made from identified SPNs projecting to or through the lumbar sympathetic chain between L4 and L5 ganglia, and from caudal raphe neurones with axons projecting to the spinal cord. The respiratory-related firing patterns were analysed. Differences in patterns of respiratory modulation and the proportion of SPNs with a certain pattern of respiratory modulation were found between SPNs recorded in the present study and SPNs located in upper thoracic spinal segments reported previously. These findings provide an explanation of the regional differences of respiratory modulation in various sympathetic nerves. Many caudal raphe-spinal neurones with respiratory-related activity could be activated antidromically from the area of the intermediolateral cell column (IML) and activity in some of these neurons correlated to the 2 to 6 Hz rhythm of cervical sympathetic activity. The findings are consistent with the idea that caudal raphe neurones within the region from which I recorded in this study are part of a supraspinal network that contributes to the 2 to 6 Hz component of sympathetic nerve activity. Therefore some raphe-spinal neurones may relay both "respiratory" and "sympathetic" rhythmic components to the sympathetic outflow. These spinally- projecting neurones in caudal raphe nuclei are different from those in the rostral ventrolateral medulla (RVLM) as they have no baroreceptor-related activity. Additionally, they do not have the "typical" characteristics of 5-HT containing neurones which have slow conduction velocities, and slow regular firing characteristics: the majority had small myelinated axons as indicated by their conduction velocities and relatively high discharge rates and irregular firing characteristics