Electrical Activity Of Neuronal Networks Research Articles

In vitro exposure of neuronal networks to the 5G-3.5 GHz signal.

The current deployment of the fifth generation (5G) of wireless communications raises new questions about the potential health effects of exposure to radiofrequency (RF) fields. So far, most of the established biological effects of RF have been known to be caused by heating. We previously reported inhibition of the spontaneous electrical activity of neuronal networks in vitro when exposed to 1.8 GHz signals at specific absorption rates (SAR) well above the guidelines. The present study aimed to assess the effects of RF fields at 3.5 GHz, one of the frequencies related to 5G, on neuronal activity in-vitro. Potential differences in the effects elicited by continuous-wave (CW) and 5G-modulated signals were also investigated. Spontaneous activity of neuronal cultures from embryonic cortices was recorded using 60-electrode multi-electrode arrays (MEAs) between 17 and 27 days in vitro. The neuronal cultures were subjected to 15 min RF exposures at SAR of 1, 3, and 28 W/kg. At SAR close to the guidelines (1 and 3 W/kg), we found no conclusive evidence that 3.5 GHz RF exposure impacts the activity of neurons in vitro. On the contrary, CW and 5G-modulated signals elicited a clear decrease in bursting and total firing rates during RF exposure at high SAR levels (28 W/kg). Our experimental findings extend our previous results, showing that RF, at 1.8 to 3.5 GHz, inhibits the electrical activity of neurons in vitro at levels above environmental standards.

Investigating Peripheral Regional Anesthesia Using Induced Pluripotent Stem Cell Technology: Exploring Novel Terrain.

Investigating Peripheral Regional Anesthesia Using Induced Pluripotent Stem Cell Technology: Exploring Novel Terrain.

CoreNEURON : An Optimized Compute Engine for the NEURON Simulator.

The NEURON simulator has been developed over the past three decades and is widely used by neuroscientists to model the electrical activity of neuronal networks. Large network simulation projects using NEURON have supercomputer allocations that individually measure in the millions of core hours. Supercomputer centers are transitioning to next generation architectures and the work accomplished per core hour for these simulations could be improved by an order of magnitude if NEURON was able to better utilize those new hardware capabilities. In order to adapt NEURON to evolving computer architectures, the compute engine of the NEURON simulator has been extracted and has been optimized as a library called CoreNEURON. This paper presents the design, implementation, and optimizations of CoreNEURON. We describe how CoreNEURON can be used as a library with NEURON and then compare performance of different network models on multiple architectures including IBM BlueGene/Q, Intel Skylake, Intel MIC and NVIDIA GPU. We show how CoreNEURON can simulate existing NEURON network models with 4–7x less memory usage and 2–7x less execution time while maintaining binary result compatibility with NEURON.

Decreased spontaneous electrical activity in neuronal networks exposed to radiofrequency 1,800 MHz signals

The rapid development of wireless communications has raised questions about their potential health risks. So far, the only identified biological effects of radiofrequency fields (RF) are known to be caused by heating, but the issue of potential nonthermal biological effects, especially on the central nervous system (CNS), remains open. We previously reported a decrease in the firing and bursting rates of neuronal cultures exposed to a Global System for Mobile (GSM) RF field at 1,800 MHz for 3 min (Moretti D, Garenne A, Haro E, Poulleier de Gannes F, Lagroye I, Lévêque P, Veyret B, Lewis N. Bioelectromagnetics 34: 571-578, 2013). The aim of the present work was to assess the dose-response relationship for this effect and also to identify a potential differential response elicited by pulse-modulated GSM and continuous-wave (CW) RF fields. Spontaneous bursting activity of neuronal cultures from rat embryonic cortices was recorded using 60-electrode multielectrode arrays (MEAs). At 17-28 days in vitro, the neuronal cultures were subjected to 15-min RF exposures, at specific absorption rates (SAR) ranging from 0.01 to 9.2 W/kg. Both GSM and CW signals elicited a clear decrease in bursting rate during the RF exposure phase. This effect became more marked with increasing SAR and lasted even beyond the end of exposure for the highest SAR levels. Moreover, the amplitude of the effect was greater with the GSM signal. Altogether, our experimental findings provide evidence for dose-dependent effects of RF signals on the bursting rate of neuronal cultures and suggest that part of the mechanism is nonthermal. NEW & NOTEWORTHY In this study, we investigated the effects of some radiofrequency (RF) exposure parameters on the electrical activity of neuronal cultures. We detected a clear decrease in bursting activity, dependent on exposure duration. The amplitude of this effect increased with the specific absorption rate (SAR) level and was greater with Global System for Mobile signal than with continuous-wave signal, at the same average SAR. Our experiment provides unique evidence of a decrease in electrical activity of cortical neuronal cultures during RF exposure.

Development of a 3D in vitro platform for functional and structural interrogation of neuronal circuits

Development of a 3D in vitro platform for functional and structural interrogation of neuronal circuits

(Invited) Carbon-Based Nanomaterials for Bioelectronics

Carbon-based nanomaterials, such as carbon nanotubes (CNTs) and graphene, have gained significant interest as one of the most promising materials in biological applications due to their unique physical and chemical properties. Recently we have developed an optoelectronic probing system, combining CNT/graphene transistors with scanning photocurrent measurements, fluorescence microscopy, and optical trapping techniques to investigate the molecular interface between CNTs/graphene and biological systems. Here, optical tweezers have been used to manipulate individual DNA molecules with sub-piconewton force precision and to directly measure the binding force between a DNA molecule and a CNT. Three-dimensional scanning photocurrent microscopy has been utilized to monitor the morphology changes of CNTs, allowing for a comprehensive reconstruction of the CNT-DNA interaction dynamics. We have also integrated graphene-based scanning photocurrent microscopy with microfluidic platforms to study the electrical activity in neuronal networks. These fundamental studies not only provide a new platform for exploring mechanical and electrical coupling at nanobio-interfaces, but also shed light on new design rules for future nanobioelectronics.

Optical Recording of Voltage Activation of Endogenous Potassium Channels

Diverse cellular electrical signals are conducted by a vast array of ion channel types acting in concert. The spatial and temporal contributions of specific voltage gated ion channels to neuronal electrical signaling are challenging to establish. We have developed fluorescent probes that indicate when and where Kv2 voltage gated potassium channels are activated by voltage. These ion channel activity probes are engineered from tarantula toxins that bind Kv2 channel voltage sensors at rest, and dissociate when the channels are voltage activated. Previously, we found ion channel activity probes to detect overexpressed Kv2 ion channels. Here, we explore their ability to identify activation of endogenous neuronal ion channels. In rat hippocampal slices and dissociated neurons, we find that exogenously applied Kv2 ion channel probes label punctate structures on neuronal cell bodies similar to endogenous Kv2 ion channels. In neurons transfected with GFP-Kv2.1, ion channel probe puncta colocalize with GFP puncta. Depolarizing stimuli that induce Kv2 channel activation, trigger dissipation of fluorescent puncta from neurons. Together, our results suggest that ion channel probes can identify the locations of specific ion channel types in living neurons, and report when and where the channels are activated by voltage. Further development of probes that target to select conformations of ion channels could enable imaging of the contributions of specific ion channel types to electrical activity in neuronal networks.

The effect of hyperbaric air on the electric activity of neuronal in vitro networks.

Breathing hyperbaric air or gas mixtures, for example during diving or when working underwater is known to alter the electrophysiological behavior of neuronal cells, which may lead to restricted cognition. During the last few decades, only very few studies into hyperbaric effects have been published, especially for the most relevant pressure range of up to 10 bar. We designed a pressurized measuring chamber to record pressure effects on the electrical activity of neuronal networks formed by primary cells of the frontal cortex of NMRI mice. Electrical activity was recorded with multi-electrode arrays (MEAs) of glass neuro chips while subjected to a step-by-step pressure increase from atmospheric pressure (1 bar) to 2 and 4 bar, followed by a decompression to 1 bar, in order to record recovery effects. The effects of pressure on the total spike rates (TSRs), which were averaged from at least 45 chips, were detected in two cell culture media with different compositions. In a DMEM medium with 6% horse serum, the TSR was increased by 19% after a pressure increase to 2 bar and remained stable at 4 bar. In NMEM medium with 2% B27, the TSR was not altered by a pressure increase to 2 bar but increased by 9% at 4 bar. After decompression to 1 bar, the activities decreased to 76% and 101% of their respective control levels in the two media. MEA recordings from neuronal networks in miniaturized hyperbaric measuring chambers provide new access for exploring the neuronal effects of hyperbaric breathing gases.

Rhythms and blues: modulation of oscillatory synchrony and the mechanism of action of antidepressant treatments.

Treatments for major depressive disorder (MDD) act at different hierarchical levels of biological complexity, ranging from the individual synapse to the brain as a whole. Theories of antidepressant medication action traditionally have focused on the level of cell-to-cell interaction and synaptic neurotransmission. However, recent evidence suggests that modulation of synchronized electrical activity in neuronal networks is a common effect of antidepressant treatments, including not only medications, but also neuromodulatory treatments such as repetitive transcranial magnetic stimulation. Synchronization of oscillatory network activity in particular frequency bands has been proposed to underlie neurodevelopmental and learning processes, and also may be important in the mechanism of action of antidepressant treatments. Here, we review current research on the relationship between neuroplasticity and oscillatory synchrony, which suggests that oscillatory synchrony may help mediate neuroplastic changes related to neurodevelopment, learning, and memory, as well as medication and neuromodulatory treatment for MDD. We hypothesize that medication and neuromodulation treatments may have related effects on the rate and pattern of neuronal firing, and that these effects underlie antidepressant efficacy. Elucidating the mechanisms through which oscillatory synchrony may be related to neuroplasticity could lead to enhanced treatment strategies for MDD.

In‐vitro exposure of neuronal networks to the GSM‐1800 signal

The central nervous system is the most likely target of mobile telephony radiofrequency (RF) field exposure in terms of biological effects. Several electroencephalography (EEG) studies have reported variations in the alpha-band power spectrum during and/or after RF exposure, in resting EEG and during sleep. In this context, the observation of the spontaneous electrical activity of neuronal networks under RF exposure can be an efficient tool to detect the occurrence of low-level RF effects on the nervous system. Our research group has developed a dedicated experimental setup in the GHz range for the simultaneous exposure of neuronal networks and monitoring of electrical activity. A transverse electromagnetic (TEM) cell was used to expose the neuronal networks to GSM-1800 signals at a SAR level of 3.2 W/kg. Recording of the neuronal electrical activity and detection of the extracellular spikes and bursts under exposure were performed using microelectrode arrays (MEAs). This work provides the proof of feasibility and preliminary results of the integrated investigation regarding exposure setup, culture of the neuronal network, recording of the electrical activity, and analysis of the signals obtained under RF exposure. In this pilot study on 16 cultures, there was a 30% reversible decrease in firing rate (FR) and bursting rate (BR) during a 3 min exposure to RF. Additional experiments are needed to further characterize this effect.

Nanoparticles Induce Changes of the Electrical Activity of Neuronal Networks on Microelectrode Array Neurochips

BackgroundNanomaterials are extensively used in industry and daily life, but little is known about possible health effects. An intensified research regarding toxicity of nanomaterials is urgently needed. Several studies have demonstrated that nanoparticles (NPs; diameter < 100 nm) can be transported to the central nervous system; however, interference of NPs with the electrical activity of neurons has not yet been shown.Objectives/methodsWe investigated the acute electrophysiological effects of carbon black (CB), hematite (Fe2O3), and titanium dioxide (TiO2) NPs in primary murine cortical networks on microelectrode array (MEA) neurochips. Uptake of NPs was studied by transmission electron microscopy (TEM), and intracellular formation of reactive oxygen species (ROS) was studied by flow cytometry.ResultsThe multiparametric assessment of electrical activity changes caused by the NPs revealed an NP-specific and concentration-dependent inhibition of the firing patterns. The number of action potentials and the frequency of their patterns (spike and burst rates) showed a significant particle-dependent decrease and significant differences in potency. Further, we detected the uptake of CB, Fe2O3, and TiO2 into glial cells and neurons by TEM. Additionally, 24 hr exposure to TiO2 NPs caused intracellular formation of ROS in neuronal and glial cells, whereas exposure to CB and Fe2O3 NPs up to a concentration of 10 μg/cm2 did not induce significant changes in free radical levels.ConclusionNPs at low particle concentrations are able to exhibit a neurotoxic effect by disturbing the electrical activity of neuronal networks, but the underlying mechanisms depend on the particle type.

Role of interneuronal systems in the formation of main patterns of field electrical activity in the hippocampus

Studies on the cellular and subcellular levels promote elucidation of the fundamental principles of formation of effective neuronal systems from cell units. To estimate the interrelations between electrical activity of neuronal networks and processes realized on the cellular level, we need to adequately understand the general patterns of behavior of populations of interneurons, which are components of these networks, under different physiological conditions. In this review, we describe and discuss the relations between the electrical activity of single hippocampal neurons and different components of the field electrical activity, as well as modern concepts on the mode of involvement of the system of hippocampal interneurons in the formation of physiologically important patterns of efferent activity of the above-mentioned structure (in particular in encoding of information on the neuronal level).

On the Dynamics of the Spontaneous Activity in Neuronal Networks

Most neuronal networks, even in the absence of external stimuli, produce spontaneous bursts of spikes separated by periods of reduced activity. The origin and functional role of these neuronal events are still unclear. The present work shows that the spontaneous activity of two very different networks, intact leech ganglia and dissociated cultures of rat hippocampal neurons, share several features. Indeed, in both networks: i) the inter-spike intervals distribution of the spontaneous firing of single neurons is either regular or periodic or bursting, with the fraction of bursting neurons depending on the network activity; ii) bursts of spontaneous spikes have the same broad distributions of size and duration; iii) the degree of correlated activity increases with the bin width, and the power spectrum of the network firing rate has a 1/f behavior at low frequencies, indicating the existence of long-range temporal correlations; iv) the activity of excitatory synaptic pathways mediated by NMDA receptors is necessary for the onset of the long-range correlations and for the presence of large bursts; v) blockage of inhibitory synaptic pathways mediated by GABAA receptors causes instead an increase in the correlation among neurons and leads to a burst distribution composed only of very small and very large bursts. These results suggest that the spontaneous electrical activity in neuronal networks with different architectures and functions can have very similar properties and common dynamics.

Long term behavior of lithographically prepared in vitro neuronal networks.

We measured the long term spontaneous electrical activity of neuronal networks with different sizes, grown on lithographically prepared substrates and recorded with multi-electrode-array technology. The time sequences of synchronized bursting events were used to characterize network dynamics. All networks exhibit scale-invariant Lévy distributions and long-range correlations. These observations suggest that different-size networks self-organize to adjust their activities over many time scales. As predictions of current models differ from our observations, this calls for revised models.