scholarly journals Cortical spike multiplexing using gamma frequency latencies

2018 ◽  
Author(s):  
Dana H. Ballard ◽  
Ruohan Zhang
Keyword(s):  
Action Potentials ◽  
New Technologies ◽  
Signal Transmission ◽  
Cortical Cell ◽  
General Purpose ◽  
Spike Timing ◽  
Population Coding ◽  
Cortical Cells ◽  
Gamma Frequency

AbstractOne of the fundamental problems in understanding the brain, in particular the cerebral cortex, is that we only have a partial understanding of the basic communication protocols that underlie signal transmission. This makes it difficult to interpret the significance of particular phenomena such as basic firing patterns and oscillations at different frequencies. There are, of course, useful models. Motivated by single-cell recording technology, Poisson statistics of cortical action potentials have long been a basic component in models of signal representation in the cortex. However, it is increasingly difficult to integrate Poisson spiking with spike timing signals in the gamma frequency spectrum. A potential way forward is being sparked by new technologies that allow the exploration of very low-level communication strategies. Specifically, the voltage potential of a cell’s soma now can be recorded with very high fidelity in vivo, allowing correlation of its fine structure to be correlated with behaviors. To interpret this data, we have developed a unified model (gamma spike multiplexing, or GSM) wherein a cell’s somatic gamma frequencies can modulate the generation of action potentials. Such spikes can be seen as the basis for a general-purpose method of modulating fast communication in cortical networks. In particular, the model has several important advantages over traditional formalisms: 1) It allows multiple, independent processes to run in parallel, greatly increasing the processing capability of the cortex 2) Its processing speed is 102 to 103 times faster than population coding methods 3) Its processes are not bound to specific locations, but migrate across cortical cells as a function of time, facilitating the maintenance of cortical cell calibration.

Synaptic and intrinsic responses of medical entorhinal cortical cells in normal and magnesium-free medium in vitro

1988 ◽  
Vol 59 (5) ◽  
pp. 1476-1496 ◽  
Author(s):  
R. S. Jones ◽  
U. Heinemann
Keyword(s):  
Entorhinal Cortex ◽  
Action Potentials ◽  
Membrane Conductance ◽  
Nmda Receptor Antagonist ◽  
Field Potentials ◽  
Cortical Cells ◽  
Medial Entorhinal Cortex ◽  
Membrane Hyperpolarization

1. Extracellular recordings were made from slices of hippocampus plus parahippocampal regions maintained in vitro. Field potentials, recorded in the entorhinal cortex after stimulation in the subiculum, resembled those observed in vivo. 2. Washout of magnesium from the slices resulted in paroxysmal events which resembled those occurring during sustained seizures in vivo. These events were greatest in amplitude and duration in layers IV/V of the medial entorhinal cortex and could occur both spontaneously and in response to subicular stimulation. Spontaneous seizure-like events were not prevented by severing the connections between the hippocampus and entorhinal cortex, but much smaller and shorter events occurring in the dentate gyrus were stopped by this manipulation. Both spontaneous and evoked paroxysmal events were blocked by perfusion with the N-methyl-D-aspartate (NMDA) receptor antagonist, DL-2-amino-5-phosphonovalerate (2-AP5). 3. Neurons in layers IV/V were characterized by intracellular recording. Injection of depolarizing current in most cells evoked a train of nondecrementing action potentials with only weak spike frequency accommodation and little or no posttrain after hyperpolarization. 4. A small number of cells displayed burst response when depolarized by positive current. The burst consisted of a slow depolarization with superimposed action potentials which decreased in amplitude and increased in duration during the discharge. The burst was terminated by a strong after hyperpolarization and thereafter, during prolonged current pulses a train of nondecrementing spikes occurred. The burst response remained if the cell was held at hyperpolarized levels but was inactivated by holding the cell at a depolarized level. 5. Depolarizing synaptic potentials could be evoked by stimulation in the subiculum. A delayed and prolonged depolarization clearly decremented with membrane hyperpolarization and, occasionally, increased with depolarization. 6. Washout of magnesium from the slices resulted in an enhancement of the late depolarization and a reversal of its voltage dependence. Eventually a single shock to the subiculum evoked a large all-or-none paroxysmal depolarization associated with a massive increase in membrane conductance. Similar events occurred spontaneously in all cells tested. The paroxysmal depolarizations, both spontaneous and evoked, were rapidly blocked by 2-AP5. 7. It is concluded that medial entorhinal cortical cells possess several intrinsic and synaptic properties which confer an extreme susceptibility to generation of sustained seizure activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Excitation and inhibition in orientation selectivity of cat visual cortex neurons revealed by whole-cell recordings in vivo

1993 ◽  
Vol 10 (6) ◽  
pp. 1151-1155 ◽  
Author(s):  
M. Volgushev ◽  
Xing Pei ◽  
T. R. Vidyasagar ◽  
O. D. Creutzfeldt
Keyword(s):  
Striate Cortex ◽  
Cortical Cell ◽  
Orientation Selectivity ◽  
Cortical Cells ◽  
Whole Cell ◽  
Degree Of Orientation ◽  
Visual Cortex Neurons ◽  
High Degree ◽  
Whole Cell Recordings

AbstractOne striking transformation in response properties that occurs in the geniculo-cortical pathway is the appearance of a high degree of orientation selectivity in the cortex. This property may be conceived as arising purely from the excitatory inputs to the cell, as being structured largely by the inhibition a cortical cell receives or could be due to a combination of the two. We have studied the contributions of excitatory and inhibitory inputs to cortical cells' orientation selectivity by analyzing the postsynaptic potentials evoked in cat striate neurones by flashing stimuli of different orientations. We made these recordings using the in vivo whole-cell technique (Xing Pei et al., 1991), which provides more stable and reliable results than classical intracellular recording methods. Our results show that the cat striate cortex exhibits a variety of mechanisms to achieve orientation selectivity. Orientation selectivity of a particular cell can be created by excitatory, by inhibitory, or by a combination of both mechanisms.

Phasic Stimuli Evoke Precisely Timed Spikes in Intermittently Discharging Mitral Cells

2004 ◽  
Vol 92 (2) ◽  
pp. 743-753 ◽  
Author(s):  
Ramani Balu ◽  
Phillip Larimer ◽  
Ben W. Strowbridge
Keyword(s):  
Olfactory Bulb ◽  
Action Potentials ◽  
Sensory Stimulation ◽  
Spike Timing ◽  
Mitral Cells ◽  
Potential Oscillations ◽  
Sensory Stimuli ◽  
Subthreshold Oscillations ◽  
Simple Step

Mitral cells, the principal cells of the olfactory bulb, respond to sensory stimulation with precisely timed patterns of action potentials. By contrast, the same neurons generate intermittent spike clusters with variable timing in response to simple step depolarizations. We made whole cell recordings from mitral cells in rat olfactory bulb slices to examine the mechanisms by which normal sensory stimuli could generate precisely timed spike clusters. We found that individual mitral cells fired clusters of action potentials at 20-40 Hz, interspersed with periods of subthreshold membrane potential oscillations in response to depolarizing current steps. TTX (1 μM) blocked a sustained depolarizing current and fast subthreshold oscillations in mitral cells. Phasic stimuli that mimic trains of slow excitatory postsynaptic potentials (EPSPs) that occur during sniffing evoked precisely timed spike clusters in repeated trials. The amplitude of the first simulated EPSP in a train gated the generation of spikes on subsequent EPSPs. 4-aminopyridine (4-AP)–sensitive K+ channels are critical to the generation of spike clusters and reproducible spike timing in response to phasic stimuli. Based on these results, we propose that spike clustering is a process that depends on the interaction between a 4-AP–sensitive K+ current and a subthreshold TTX-sensitive Na+ current; interactions between these currents may allow mitral cells to respond selectively to stimuli in the theta frequency range. These intrinsic properties of mitral cells may be important for precisely timing spikes evoked by phasic stimuli that occur in response to odor presentation in vivo.

Parallel Neural Multiprocessing with Gamma Frequency Latencies

2020 ◽  
Vol 32 (9) ◽  
pp. 1635-1663
Author(s):  
Ruohan Zhang ◽  
Dana H. Ballard
Keyword(s):  
Cortical Cell ◽  
Spike Timing ◽  
System Level ◽  
Neural Responses ◽  
Gamma Frequency ◽  
Neural Processes ◽  
Rate Coding ◽  
Millisecond Range ◽  
Cortex System ◽  
Cell Data

The Poisson variability in cortical neural responses has been typically modeled using spike averaging techniques, such as trial averaging and rate coding, since such methods can produce reliable correlates of behavior. However, mechanisms that rely on counting spikes could be slow and inefficient and thus might not be useful in the brain for computations at timescales in the 10 millisecond range. This issue has motivated a search for alternative spike codes that take advantage of spike timing and has resulted in many studies that use synchronized neural networks for communication. Here we focus on recent studies that suggest that the gamma frequency may provide a reference that allows local spike phase representations that could result in much faster information transmission. We have developed a unified model (gamma spike multiplexing) that takes advantage of a single cycle of a cell's somatic gamma frequency to modulate the generation of its action potentials. An important consequence of this coding mechanism is that it allows multiple independent neural processes to run in parallel, thereby greatly increasing the processing capability of the cortex. System-level simulations and preliminary analysis of mouse cortical cell data are presented as support for the proposed theoretical model.

Meiotic CENP-C is a shepherd: bridging the space between the centromere and the kinetochore in time and space

2020 ◽  
Vol 64 (2) ◽  
pp. 251-261
Author(s):  
Jessica E. Fellmeth ◽  
Kim S. McKim
Keyword(s):  
Chromosome Segregation ◽  
New Technologies ◽  
Early Prophase ◽  
Unique Role ◽  
Kinetochore Assembly ◽  
M Phase ◽  
In Vivo Analysis ◽  
Meiosis I

Abstract While many of the proteins involved in the mitotic centromere and kinetochore are conserved in meiosis, they often gain a novel function due to the unique needs of homolog segregation during meiosis I (MI). CENP-C is a critical component of the centromere for kinetochore assembly in mitosis. Recent work, however, has highlighted the unique features of meiotic CENP-C. Centromere establishment and stability require CENP-C loading at the centromere for CENP-A function. Pre-meiotic loading of proteins necessary for homolog recombination as well as cohesion also rely on CENP-C, as do the main scaffolding components of the kinetochore. Much of this work relies on new technologies that enable in vivo analysis of meiosis like never before. Here, we strive to highlight the unique role of this highly conserved centromere protein that loads on to centromeres prior to M-phase onset, but continues to perform critical functions through chromosome segregation. CENP-C is not merely a structural link between the centromere and the kinetochore, but also a functional one joining the processes of early prophase homolog synapsis to late metaphase kinetochore assembly and signaling.

The Synergy between CRISPR and Chemical Engineering

2019 ◽  
Vol 19 (3) ◽  
pp. 147-171
Author(s):  
Cia-Hin Lau ◽  
Chung Tin
Keyword(s):  
Viral Vectors ◽  
Chemical Engineering ◽  
Target Genes ◽  
New Technologies ◽  
Rapid Development ◽  
Genetic Circuits ◽  
Viral Packaging ◽  
Conditional Control ◽  
Logic Operations

Gene therapy and transgenic research have advanced quickly in recent years due to the development of CRISPR technology. The rapid development of CRISPR technology has been largely benefited by chemical engineering. Firstly, chemical or synthetic substance enables spatiotemporal and conditional control of Cas9 or dCas9 activities. It prevents the leaky expression of CRISPR components, as well as minimizes toxicity and off-target effects. Multi-input logic operations and complex genetic circuits can also be implemented via multiplexed and orthogonal regulation of target genes. Secondly, rational chemical modifications to the sgRNA enhance gene editing efficiency and specificity by improving sgRNA stability and binding affinity to on-target genomic loci, and hence reducing off-target mismatches and systemic immunogenicity. Chemically-modified Cas9 mRNA is also more active and less immunogenic than the native mRNA. Thirdly, nonviral vehicles can circumvent the challenges associated with viral packaging and production through the delivery of Cas9-sgRNA ribonucleoprotein complex or large Cas9 expression plasmids. Multi-functional nanovectors enhance genome editing in vivo by overcoming multiple physiological barriers, enabling ligand-targeted cellular uptake, and blood-brain barrier crossing. Chemical engineering can also facilitate viral-based delivery by improving vector internalization, allowing tissue-specific transgene expression, and preventing inactivation of the viral vectors in vivo. This review aims to discuss how chemical engineering has helped improve existing CRISPR applications and enable new technologies for biomedical research. The usefulness, advantages, and molecular action for each chemical engineering approach are also highlighted.

Stress Field Around a Large Opening in a Pressure Vessel During a Major Repair

2009 ◽  
Author(s):  
Erik Garrido ◽  
Euro Casanova
Keyword(s):  
Pressure Vessel ◽  
New Technologies ◽  
Mechanical Design ◽  
General Purpose ◽  
Pressure Vessels ◽  
Mechanical Equipment ◽  
Stress Distributions ◽  
Large Opening ◽  
Von Mises ◽  
Case Basis

It is a regular practice in the oil industry to modify mechanical equipment to incorporate new technologies and to optimize production. In the case of pressure vessels, it is occasionally required to cut large openings in their walls in order to have access to the interior part of the equipment for executing modifications. This cutting process produces temporary loads, which were obviously not considered in the original mechanical design. Up to now, there is not a general purpose specification for approaching the assessments of stress levels once a large opening in a vertical pressure vessel has been made. Therefore stress distributions around large openings are analyzed on a case-by-case basis without a reference scheme. This work studies the distribution of the von Mises equivalent stresses around a large opening in FCC Regenerators during internal cyclone replacement, which is a frequently required practice for this kind of equipment. A finite element parametric model was developed in ANSYS, and both numerical results and illustrating figures are presented.

scholarly journals Interhelical H-Bonds Modulate the Activity of a Polytopic Transmembrane Kinase

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 938
Author(s):  
Juan Cruz Almada ◽  
Ana Bortolotti ◽  
Jean Marie Ruysschaert ◽  
Diego de Mendoza ◽  
María Eugenia Inda ◽  
...  
Keyword(s):  
Histidine Kinase ◽  
Adaptive Response ◽  
Catalytic Domain ◽  
Membrane Lipids ◽  
Signal Transmission ◽  
Expression System ◽  
Lipid Homeostasis ◽  
Transmembrane Helices ◽  
Transmembrane Region

DesK is a Histidine Kinase that allows Bacillus subtilis to maintain lipid homeostasis in response to changes in the environment. It is located in the membrane, and has five transmembrane helices and a cytoplasmic catalytic domain. The transmembrane region triggers the phosphorylation of the catalytic domain as soon as the membrane lipids rigidify. In this research, we study how transmembrane inter-helical interactions contribute to signal transmission; we designed a co-expression system that allows studying in vivo interactions between transmembrane helices. By Alanine-replacements, we identified a group of polar uncharged residues, whose side chains contain hydrogen-bond donors or acceptors, which are required for the interaction with other DesK transmembrane helices; a particular array of H-bond- residues plays a key role in signaling, transmitting information detected at the membrane level into the cell to finally trigger an adaptive response.

scholarly journals A predictive in vitro risk assessment platform for pro-arrhythmic toxicity using human 3D cardiac microtissues

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Celinda M. Kofron ◽  
Tae Yun Kim ◽  
Fabiola Munarin ◽  
Arvin H. Soepriatna ◽  
Rajeev J. Kant ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Action Potentials ◽  
Induced Pluripotent Stem Cell ◽  
Human Action ◽  
Environmental Toxicants ◽  
Pharmaceutical Drugs ◽  
Industrial Chemicals ◽  
Endocrine Disrupting Chemical

AbstractCardiotoxicity of pharmaceutical drugs, industrial chemicals, and environmental toxicants can be severe, even life threatening, which necessitates a thorough evaluation of the human response to chemical compounds. Predicting risks for arrhythmia and sudden cardiac death accurately is critical for defining safety profiles. Currently available approaches have limitations including a focus on single select ion channels, the use of non-human species in vitro and in vivo, and limited direct physiological translation. We have advanced the robustness and reproducibility of in vitro platforms for assessing pro-arrhythmic cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes and human cardiac fibroblasts in 3-dimensional microtissues. Using automated algorithms and statistical analyses of eight comprehensive evaluation metrics of cardiac action potentials, we demonstrate that tissue-engineered human cardiac microtissues respond appropriately to physiological stimuli and effectively differentiate between high-risk and low-risk compounds exhibiting blockade of the hERG channel (E4031 and ranolazine, respectively). Further, we show that the environmental endocrine disrupting chemical bisphenol-A (BPA) causes acute and sensitive disruption of human action potentials in the nanomolar range. Thus, this novel human 3D in vitro pro-arrhythmic risk assessment platform addresses critical needs in cardiotoxicity testing for both environmental and pharmaceutical compounds and can be leveraged to establish safe human exposure levels.

scholarly journals Effects of memristive synapse radiation interactions on learning in spiking neural networks

2021 ◽  
Vol 3 (5) ◽  
Author(s):  
Sumedha Gandharava Dahl ◽  
Robert C. Ivans ◽  
Kurtis D. Cantley
Keyword(s):  
Action Potentials ◽  
Radiation Effects ◽  
Synaptic Weight ◽  
Learning Rule ◽  
Spike Timing ◽  
Spiking Neural Network ◽  
Synaptic Action ◽  
Drift Model ◽  
Spatio Temporal ◽  
Post Synaptic Neuron

AbstractThis study uses advanced modeling and simulation to explore the effects of external events such as radiation interactions on the synaptic devices in an electronic spiking neural network. Specifically, the networks are trained using the spike-timing-dependent plasticity (STDP) learning rule to recognize spatio-temporal patterns (STPs) representing 25 and 100-pixel characters. Memristive synapses based on a TiO2 non-linear drift model designed in Verilog-A are utilized, with STDP learning behavior achieved through bi-phasic pre- and post-synaptic action potentials. The models are modified to include experimentally observed state-altering and ionizing radiation effects on the device. It is found that radiation interactions tend to make the connection between afferents stronger by increasing the conductance of synapses overall, subsequently distorting the STDP learning curve. In the absence of consistent STPs, these effects accumulate over time and make the synaptic weight evolutions unstable. With STPs at lower flux intensities, the network can recover and relearn with constant training. However, higher flux can overwhelm the leaky integrate-and-fire post-synaptic neuron circuits and reduce stability of the network.

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