Recordings Of Spontaneous Activity Research Articles

A data repository and analysis framework for spontaneous neural activity recordings in developing retina

BackgroundDuring early development, neural circuits fire spontaneously, generating activity episodes with complex spatiotemporal patterns. Recordings of spontaneous activity have been made in many parts of the nervous system over the last 25 years, reporting developmental changes in activity patterns and the effects of various genetic perturbations.ResultsWe present a curated repository of multielectrode array recordings of spontaneous activity in developing mouse and ferret retina. The data have been annotated with minimal metadata and converted into HDF5. This paper describes the structure of the data, along with examples of reproducible research using these data files. We also demonstrate how these data can be analysed in the CARMEN workflow system. This article is written as a literate programming document; all programs and data described here are freely available.Conclusions1. We hope this repository will lead to novel analysis of spontaneous activity recorded in different laboratories. 2. We encourage published data to be added to the repository. 3. This repository serves as an example of how multielectrode array recordings can be stored for long-term reuse.

Fast transient networks in spontaneous human brain activity

To provide an effective substrate for cognitive processes, functional brain networks should be able to reorganize and coordinate on a sub-second temporal scale. We used magnetoencephalography recordings of spontaneous activity to characterize whole-brain functional connectivity dynamics at high temporal resolution. Using a novel approach that identifies the points in time at which unique patterns of activity recur, we reveal transient (100-200 ms) brain states with spatial topographies similar to those of well-known resting state networks. By assessing temporal changes in the occurrence of these states, we demonstrate that within-network functional connectivity is underpinned by coordinated neuronal dynamics that fluctuate much more rapidly than has previously been shown. We further evaluate cross-network interactions, and show that anticorrelation between the default mode network and parietal regions of the dorsal attention network is consistent with an inability of the system to transition directly between two transient brain states. DOI: http://dx.doi.org/10.7554/eLife.01867.001.

Development of very large electrode arrays for epiretinal stimulation (VLARS)

BackgroundRetinal implants have been developed to treat blindness causing retinal degenerations such as Retinitis pigmentosa (RP). The retinal stimulators are covering only a small portion of the retina usually in its center. To restore not only central vision but also a useful visual field retinal stimulators need to cover a larger area of the retina. However, large area retinal stimulators are much more difficult to implant into an eye. Some basic questions concerning this challenge should be answered in a series of experiments.MethodsLarge area retinal stimulators were fabricated as flexible multielectrode arrays (MEAs) using silicon technology with polyimide as the basic material for the substrate. Electrodes were made of gold covered with reactively sputtered iridium oxide. Several prototype designs were considered and implanted into enucleated porcine eyes. The prototype MEAs were also used as recording devices.ResultsLarge area retinal stimulator MEAs were fabricated with a diameter of 12 mm covering a visual angle of 37.6° in a normal sighted human eye. The structures were flexible enough to be implanted in a folded state through an insertion nozzle. The implants could be positioned onto the retinal surface and fixated here using a retinal tack. Recording of spontaneous activity of retinal neurons was possible in vitro using these devices.ConclusionsLarge flexible MEAs covering a wider area of the retina as current devices could be fabricated using silicon technology with polyimide as a base material. Principal surgical techniques were established to insert such large devices into an eye and the devices could also be used for recording of retinal neural activity.

2. Spontaneous activity in electromyography – Generators and clinical correlations

In this paper different types of spontaneous activity in electromyography are presented. Possible generators of certain types of spontaneous activity (fibrillations, positive denervation potentials, fasciculations, diplets, triplets, multiplets, myokymic discharges, complex repetitive discharges, myotonic discharges, neuromyotonic discharges, cramps) across different parts of the motor units (MU) and clinical entities and syndromes in which it may be registered. There is no unique explanation for the generators of certain types of spontaneous activity in some entities. Thus, the registration of fasciculations in ALS is associated with their multifocal origin along various parts of MU. Recording of spontaneous activity may have diagnostic and prognostic value in certain neuromuscular disorders. Thus, the expression of fibrillations (1+ to 4+) is associated with the number of denervated muscle fibers in different diseases and damage of various parts of MU (motor neuron disease, neuropathy, disorders of the neuromuscular junction, myopathies). We analyzed the possible significance of various parameters of spontaneous activity in the diagnosis and prognosis of certain entities.

Electrical coupling of mammalian neurons to microelectrodes with 3D nanoprotrusions

Ion Beam Induced Deposition (IBID) is employed to fabricate three-dimensional nanoprotrusions on top of the recording pads of an active pixel sensor array (APS-MEA) featuring 4096 microelectrodes. Modified APS-MEAs are envisioned as enhanced tools to achieve real-time “in-cell” recordings from thousands of sensing elements, thus aiming to large-scale in-vitro registrations with unprecedented signal quality. A generalized electric model is proposed to address the revealed complexity of the neuron/electrode interface, and simulations have been conducted revealing the most advantageous cell/electrode coupling conditions. Preliminary results on the recording of spontaneous activity in cultured neuronal networks by means of nanostructured microelectrodes demonstrate the compatibility of IBID technology and APS-MEA infrastructure. The interface between cultured mammalian neurons and modified microelectrodes is revealed by FIB/SEM analysis, fostering the employment of the proposed electrical model for interpretation of electrical recordings from nanostructured microelectrodes.

Ultrastructural Morphometry of the Aortic Depressor Nerves and Extrinsic Renal Nerves: Similarities and Differences between Mice and Rats

Anatomical and physiological aspects involving rats and mice have shown similarities and differences between these experimental animal models. In cardiovascular physiology research, rats are being substituted by mice since mice are more susceptible to genetic manipulation. Nevertheless, little is known about mice normal anatomy and/or physiology to allow the correct interpretation of altered responses on genetically manipulated animals. We compared morphometric ultrastructural parameters of the aortic depressor nerve (ADN) and extrinsic renal nerve (SRN) between Wistar rats and C57BL/6J mice. After spontaneous activity recordings together with the arterial pressure pulse, ADN and SRN were dissected and prepared for light and transmission electron microscopy. Morphometry was performed with an image analysis software and took into consideration the fascicle area and diameter, myelinated and unmyelinated fiber number, density, area and diameter, myelin sheath area and the g-ratio. Comparisons were made for the same nerve between mice and rats and differences were considered significant when p<0.05. Both nerves were large in rats compared to mice, as were the myelinated fibers. On the other hand, unmyelinated fibers density, size and distributions were not different between species. These results suggest physiological differences on the fast conduction fibers between species, with possible different functional role. Morphological comparisons of the quantitative composition of peripheral nerves in different species and strains are very rare. Our study contributes to a morphological understanding of important nerves related to cardiovascular reflexes in two animal models. It also presents, for the first time, ultrastructural morphometric characteristics of the ADN in mice. This data provide a morphological basis for further studies involving functional investigations for reflex regulation of circulation in experimental model of hypertension and to improved cardiovascular system knowledge.

Noise-induced hyperactivity in the inferior colliculus: its relationship with hyperactivity in the dorsal cochlear nucleus

Intense noise exposure causes hyperactivity to develop in the mammalian dorsal cochlear nucleus (DCN) and inferior colliculus (IC). It has not yet been established whether the IC hyperactivity is driven by hyperactivity from extrinsic sources that include the DCN or instead is maintained independently of this input. We have investigated the extent to which IC hyperactivity is dependent on input from the contralateral DCN by comparing recordings of spontaneous activity in the IC of noise-exposed and control hamsters before and after ablation of the contralateral DCN. One group of animals was binaurally exposed to intense sound (10 kHz, 115 dB SPL, 4 h), whereas the control group was not. Both groups were studied electrophysiologically 2-3 wk later by first mapping spontaneous activity along the tonotopic axis of the IC to confirm induction of hyperactivity. Spontaneous activity was then recorded at a hyperactive IC locus over two 30-min periods, one with DCNs intact and the other after ablation of the contralateral DCN. In a subset of animals, activity was again mapped along the tonotopic axis after the time course of the activity was recorded before and after DCN ablation. Following recordings, the brains were fixed, and histological evaluations were performed to assess the extent of DCN ablation. Ablation of the DCN resulted in major reductions of IC hyperactivity. Levels of postablation activity in exposed animals were similar to the levels of activity in the IC of control animals, indicating an almost complete loss of hyperactivity in exposed animals. The results suggest that hyperactivity in the IC is dependent on support from extrinsic sources that include and may even begin with the DCN. This finding does not rule out longer term compensatory or homeostatic adjustments that might restore hyperactivity in the IC over time.

Microneurographic identification of spontaneous activity in C-nociceptors in neuropathic pain states in humans and rats

C-nociceptors do not normally fire action potentials unless challenged by adequate noxious stimuli. However, in pathological states nociceptors may become hyperexcitable and may generate spontaneous ectopic discharges. The aim of this study was to compare rat neuropathic pain models and to assess their suitability to model the spontaneous C-nociceptor activity found in neuropathic pain patients. Studies were performed in normal rats (n = 40), healthy human subjects (n = 15), peripheral neuropathic pain patients (n = 20), and in five rat neuropathic pain models: nerve crush (n = 24), suture (n = 14), chronic constriction injury (n = 12), STZ-induced diabetic neuropathy (n = 56), and ddC-induced neuropathy (n = 15). Microneurographic recordings were combined with electrical stimulation to monitor activity in multiple C fibers. Stimulation at 0.25 Hz allowed spontaneous impulses to be identified by fluctuations in baseline latency. Abnormal latency fluctuations could be produced by several mechanisms, and spontaneous activity was most reliably identified by the presence of unexplained latency increases corresponding to two or more additional action potentials. Spontaneous activity was present in a proportion of mechano-insensitive C-nociceptors in the patients and all rat models. The three focal traumatic nerve injury models provided the highest proportion (59.5%), whereas the two polyneuropathy models had fewer (18.6%), and the patients had an intermediate proportion (33.3%). Spontaneously active mechano-sensitive C-nociceptors were not recorded. Microneurographic recordings of spontaneous activity in diseased C-nociceptors may be useful for both short- and long-term drug studies, both in animals and in humans.

Maximized directed information transfer in critical neuronal networks

Critical dynamics in complex systems emerge at the transition from random to ordered dynamics and are characterized by power-law distributions of spatial and temporal properties of system events. The occurrence of critical dynamics in neuronal networks is increasingly supported by multielectrode array recordings of spontaneous activity in organotypic cortical slice cultures [1]. System events in these neuronal networks are typically defined as activations of neuronal ensembles, or “neuronal avalanches”. Interestingly, studies associate critical neuronal network avalanche dynamics with optimized information transfer [1,2]. However, studies have not previously examined the directed nature of information transfer in these networks. Here, we present three novel transfer-entropy [3] based measures of directed information transfer between neuronal avalanches. Our measures compute the amount of predictive information present in avalanches properties (avalanche size, avalanche duration and inter-avalanche period) of the source region about avalanche properties of the destination region and are suitable for detecting information transfer at multiple spatial scales, from individual neurons to neuronal ensembles. We apply these measures to compute directed information transfer in large, sparse, modular networks of leaky integrate-and-fire neurons with spike timing-dependent synaptic plasticity and axonal conduction delays. We characterize dynamics in our networks by distributions of neuronal avalanches and assess these distributions for power-law scaling. We compute directed information transfer between two halves of each network, and we normalize this transfer by the null-model transfer, generated by randomly rotating avalanche times for each avalanche vector, and so destroying any present relationships between groups of vectors. Dynamics in our networks change from subcritical to critical to supercritical as the modular topology of the networks is progressively randomized (Fig. ​(Fig.1a).1a). All three measures peak at criticality in all examined networks (Fig 1b-d) and hence show that directed neuronal information transfer is maximized at criticality in our model. These findings pave the way for the application of our measures to empirical multielectrode recording data. Figure 1 Directed information transfer at criticality. Fig 1A shows the presence of critical dynamics as a function of network randomization; p-values that exceed 0.5 imply power-law distributions of avalanches. Fig 1B-D show our normalized directed information ...

Effects of extremely low frequency magnetic fields on neuronal development of P19 embryonal carcinoma cells

AbstractModulation of pluripotent stem cell differentiation by several environmental factors, such as physical stimulation, is an important theme in tissue engineering. In this study, we report the effects of extremely low frequency magnetic field (ELF‐MF) exposure on the neuronal differentiation ability of P19 embryonal carcinoma cells (P19 cells). Here, the embryoid bodies (EBs) formed during the induction process were exposed to two types of ELF‐MFs (1 or 10 mT, 50 Hz, sinusoidal). After the induction process, the effects on the development of neuronal cells were evaluated by phase‐contrast image analysis, immunohistochemical staining (MAP2, GFAP), and the extracellular recording of spontaneous activity in which microelectrode arrays (MEAs) were used. Results show that MAP2 positive cells and spike frequencies increased by 10 mT ELF‐MF exposure, but the percentage of neurite outgrowth decreased at the early stages of differentiation. In contrast, clear differences were not seen in 1 mT ELF‐MF exposed cells. These results suggest that the neuronal differentiation and network properties were affected by 10 mT ELF‐MF exposure and that the intensity of the magnetic field was one of the important factors in the neuronal development of P19 cells. © 2011 Institute of Electrical Engineers of Japan. Published by John Wiley &amp; Sons, Inc.

Recording of Spontaneous Activity in Cultured Superior Colliculus Slices Using Microelectrode Array

Retino-tectal projection is one of the pathways in visual information processing. During development, spontaneous electrical activity of superior colliculus (SC) probably plays an important role for proper network formation. In this study, SC slices were taken from new-born rats and cultured on microelectrode-array (MEA) substrates. Spontaneous activities of the cultured SC were recorded for four weeks. During the first week, most of the cultured SC slices generated sporadic spikes. These sporadic spikes gradually changed into periodic synchronized bursts. Spatially organized synchronized activity produced low frequency signals (local field potential: LFP). All of the test slices showed clear LFPs within three weeks. Large negative peaks were observed in the middle layer of the slices, while positive signals were obtained around the deep layers. Current source density (CSD) analysis revealed that middle layers acted as a current source and surface and deep layers were the sinks. These results suggested that layered structures of SC were well-maintained under the culture conditions and the cells in the middle layers played dominant roles in generating these periodic synchronized spontaneous activities.

Spontaneous Calcium Changes in Micro Neuronal Networks

We have developed a practical experimental method to mass-produce and maintain a variation of minimal neuronal networks (“micro neuronal networks”) consisted of a single to several neurons in culture using spray-patterning technique. In this paper, we could maintain the micro-cultures for one month or more by adding conditioned medium and carried out optical recording of spontaneous activity in micro neuronal networks and considered the interactions between them. To determine the interactions between micro neuronal networks, fluorescence changes in several small networks were simultaneously measured using calcium indicator dye fluo-4 AM, and time-series analysis was carried out using surrogate arrangements. By using the spray-patterning method, a large number of cell-adhesive micro regions were formed. Neurons extended neurites along the edge of the cell-adhesive micro regions and form micro neuronal networks. In part of micro regions, some neurite was protruded from the region, and thus micro neuronal networks were connected with synapses. In these networks, a single neuron-induced network activity was observed. On the other hand, even in morphologically non-connected micro neuronal networks, synchronous oscillations between micro neuronal networks were observed. Our micro-patterning methods and results provide the possibility that synchronous activity is occurred between morphologically non-connected neuronal networks. This suggest that the humoral factor is also a important component for network-wide dynamics.

A ‘SIC’ and painful story

A ‘SIC’ and painful story

Differences in in vitro cerebellar neuronal responses to hypoxia in eider ducks, chicken and rats

Ducks are well-known to be more tolerant to asphyxia than non-diving birds, but it is not known if their defences include enhanced neuronal hypoxia tolerance. To test this, we compared extracellular recordings of spontaneous activity in the Purkinje cell layer of 400 mum thick isolated cerebellar slices from eider ducks, chickens and rats, before, during and after 60 min hypoxia (95%N(2)-5%CO(2)) or chemical anoxia (hypoxia + 2 mM NaCN). Most slices rapidly lost activity in hypoxia, with or without recovery after rinse and return to normoxia (95%O(2)-5%CO(2)), but some maintained spontaneous activity throughout the insult. Proportions of 'surviving' (i.e. recovering or active) duck slices were significantly higher than for chickens in anoxia, and relative activity levels were higher for ducks than for chickens during hypoxia, anoxia and recovery. Survival of rat slices was significantly poorer than for birds under all conditions. Results suggest that (1) duck cerebellar neurons are intrinsically more hypoxia-tolerant than chicken neurons; (2) avian neurons are more hypoxia-tolerant than rat neurons, and (3) the enhanced hypoxic tolerance of duck neurons largely depended on efficient anaerobiosis since it mainly manifested itself in chemical anoxia. Mechanisms underlying the observed differences in neuronal hypoxic responses remain to be elucidated.

Automatic spike train analysis and report generation. An implementation with R, R2HTML and STAR

Multi-electrode arrays (MEA) allow experimentalists to record extracellularly from many neurons simultaneously for long durations. They therefore often require that the data analyst spends a considerable amount of time first sorting the spikes, then doing again and again the same basic analysis on the different spike trains isolated from the raw data. This spike train analysis also often generates a considerable amount of figures, mainly diagnostic plots, that need to be stored (and/or printed) and organized for efficient subsequent use. The analysis of our data recorded from the first olfactory relay of an insect, the cockroach Periplaneta americana, has led us to settle on such “routine” spike train analysis procedures: one applied to spontaneous activity recordings, the other used with recordings where an olfactory stimulation was repetitively applied. We have developed a group of functions implementing a mixture of common and original procedures and producing graphical or numerical outputs. These functions can be run in batch mode and do moreover produce an organized report of their results in an HTML file. A R package: Spike Train Analysis with R (STAR) makes these functions readily available to the neurophysiologists community. Like R, STAR is open source and free. We believe that our basic analysis procedures are of general interest but they can also be very easily modified to suit user specific needs.

Neural Signal Manager: a collection of classical and innovative tools for multi‐channel spike train analysis

AbstractRecent developments in the neuroengineering field and the widespread use of the micro electrode arrays (MEAs) for electrophysiological investigations made available new approaches for studying the dynamics of dissociated neuronal networks as well as acute/organotypic slices maintained ex vivo. Importantly, the extraction of relevant parameters from these neural populations is likely to involve long‐term measurements, lasting from a few hours to entire days. The processing of huge amounts of electrophysiological data, in terms of computational time and automation of the procedures, is actually one of the major bottlenecks for both in vivo and in vitro recordings. In this paper we present a collection of algorithms implemented within a new software package, named the Neural Signal Manager (NSM), aimed at analyzing a huge quantity of data recorded by means of MEAs in a fast and efficient way. The NSM offers different approaches for both spike and burst analysis, and integrates state‐of‐the‐art statistical algorithms, such as the inter‐spike interval histogram or the post stimulus time histogram, with some recent ones, such as the burst detection and its related statistics. In order to show the potentialities of the software, the application of the developed algorithms to a set of spontaneous activity recordings from dissociated cultures at different ages is presented in the Results section. Copyright © 2008 John Wiley &amp; Sons, Ltd.

Leader neurons in population bursts of 2D living neural networks

Eytan and Marom (2006 J. Neurosci. 26 8465–76) recently showed that the spontaneous bursting activity of rat neuron cultures includes ‘first-to-fire’ cells that consistently fire earlier than others. Here, we analyze the behavior of these neurons in long-term recordings of spontaneous activity of rat hippocampal and rat cortical neuron cultures from three different laboratories. We identify precursor events that may either subside (‘aborted bursts’) or can lead to a full-blown burst (‘pre-bursts’). We find that the activation in the pre-burst typically has a first neuron (‘leader’), followed by a localized response in its neighborhood. Locality is diminished in the bursts themselves. The long-term dynamics of the leaders is relatively robust, evolving with a half-life of 23–34 h. Stimulation of the culture alters the leader distribution, but the distribution stabilizes within about 1 h. We show that the leaders carry information about the identity of the burst, as measured by the signature of the number of spikes per neuron in a burst. The number of spikes from leaders in the first few spikes of a precursor event is furthermore shown to be predictive with regard to the transition into a burst (pre-burst versus aborted burst). We conclude that the leaders play a role in the development of the bursts and conjecture that they are part of an underlying sub-network that is excited first and then acts as a nucleation center for the burst.

Electrophysiological study in the infraorbital nerve of the rat: Spontaneous and evoked activity

In this work we present some studies in the afferent nerve of the rat vibrissae. Studies on spontaneous activity (SA) in this sensorial system are of long data. Nevertheless, SA recordings in the nerve of a single vibrissa have not been made until present. In this work, we use an algorithm based on signal decomposition with Continuous Wavelet Transform (CWT) to analyse the discharges of two nerves. The action potentials of both nerves were detected and the firing rates were calculated. These results suggest that the firing rate of one vibrissa innervation is low considering that this nerve contains hundred of fibers. In addition, we present preliminary studies suggesting important effects of the hair shaft length in the afferent discharge during the vibrissae movements. The experiments consisted in recording the nerve activity after the vibrissae were sectioned at two different levels. The results showed important differences in the signal energy contents. It suggests that the hair shaft length would produce a differential activation of the mechanoreceptors located in the vibrissae follicle.

Stochastic Emergence of Repeating Cortical Motifs in Spontaneous Membrane Potential Fluctuations In Vivo

It was recently discovered that subthreshold membrane potential fluctuations of cortical neurons can precisely repeat during spontaneous activity, seconds to minutes apart, both in brain slices and in anesthetized animals. These repeats, also called cortical motifs, were suggested to reflect a replay of sequential neuronal firing patterns. We searched for motifs in spontaneous activity, recorded from the rat barrel cortex and from the cat striate cortex of anesthetized animals, and found numerous repeating patterns of high similarity and repetition rates. To test their significance, various statistics were compared between physiological data and three different types of stochastic surrogate data that preserve dynamical characteristics of the recorded data. We found no evidence for the existence of deterministically generated cortical motifs. Rather, the stochastic properties of cortical motifs suggest that they appear by chance, as a result of the constraints imposed by the coarse dynamics of subthreshold ongoing activity.

スプレーパターニングと可動式微小電極による小規模神経回路の位置選択的自発活動計測

In order to precisely grasp the self-organization process of functional neuronal circuits from individual immature neurons, electrical activity of neuronal circuits should be continuously recorded with their well-defined inner structures and boundary conditions. Standing on this viewpoint, we have developed a series of practical experimental methods for the non-invasive recording of electrical activity from cultured small neuronal circuits by combining a simple micropatterning method of cultured neurons and a site-selective extracellular recording method. The micropatterning was demonstrated with a commercially available spray, and thousands of small neuronal circuits were formed in a 35-mm polystyrene dish by spraying PDL (poly-D-lysine) solution onto the BSA (bovine serum albumin)-coated culture surface. These small neuronal circuits consisted of several neurons and kept well-patterned for more than two weeks. The site-selective recording was demonstrated by means of a handmade mobile microelectrode, and spontaneous firings were detected at multiple recording sites in a small neuronal circuit. This series of experimental methods can be directly applicable to the investigation into the developmental process of the morphology and the functions of various electrically excitable multicellular organisms.