Impact of Membrane Resistance on Width and Amplitude of Spikes in Different Injected Currents in One Spiking Neural Model

Neurons in the brain as the elementary processing units and nervous system play a key role. If a neuron gets a proper stimulus, it produces action potentials (spikes) that are transferred along its axon. Reaching the end of the neuron, other neurons or muscle cells may be activated [1]. The effect of neural morphology along with thickness of dendrites and passive electrical parameters on the spikes width and amplitude can be investigated by analytical and numerical investigations of spiking models. The impact of mentioned proper stimulus may be degraded by passing time. In this paper, it is tried to add the effective parameter ’membrane resistance’ in well-known Hodgkin-Huxley model with four dimensions to compare several outputs due to changing resistance and various injected current. The goal of this paper has been to measure spikes changes or even how to determine current threshold when resistance is not constant (non-linear time dependant) result of different factors.

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Ephaptic Coupling in Hybrid Neuronal Model

10.21203/rs.3.rs-742834/v1 ◽

2021 ◽

Author(s):

Gabriel Moreno Cunha ◽

Gilberto Corso ◽

José Garcia Vivas Miranda ◽

Gustavo Zampier Dos Santos Lima

Keyword(s):

Electric Fields ◽

Action Potentials ◽

Population Vector ◽

Input Stimulus ◽

Circular Statistic ◽

Coupling Behavior ◽

The Impact ◽

The Brain ◽

Ephaptic Coupling ◽

Phase Differences

Abstract In recent decades, there has been growing interest in the impact of electric fields generated in the brain. Transmembrane ionic currents originate electric fields in the extracellular space and are capable of affecting nearby neurons, a phenomenon called ephaptic neuronal communication. In the present work, the Quadratic Integrate-and-Trigger model (QIF-E) underwent an adjustment/improvement to include the ephaptic coupling behavior between neurons and their results are compared to the empirical results. In this way, the analysis tools are employed according to the neuronal activity regime: (i) for the subthreshold regime, the circular statistic is used to describe the phase differences between the input stimulus signal and the modeled membrane response; (ii) in the suprathreshold regime, the Population Vector and the Spike Field Coherence are employed to estimate phase preferences and the coupling intensity between the input stimulus and the Action Potentials. The results observed are i) in the subthreshold regime the values of the phase differences change with distinct frequencies of an input stimulus; ii) in the supra-threshold regime the preferential phase of Action Potentials changes for different frequencies. In addition, we explore other parameters of the model, such as noise and membrane characteristic-time, in order to understand different types of neurons and extracellular environment related to ephaptic communication. Such results are consistent with results observed in empirical experiments based on ephaptic coupling behavior. In addition, the QIF-E model allows further studies on the physiological importance of ephaptic coupling in the brain, and its simplicity can open a door to simulating ephaptic coupling in neuron networks and evaluating the impact of ephaptic communication in such scenarios.

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Modulatory Effect of Substance P to the Brain Stem Locomotor Command in Lampreys

Journal of Neurophysiology ◽

10.1152/jn.00401.2004 ◽

2005 ◽

Vol 93 (4) ◽

pp. 2127-2141 ◽

Cited By ~ 16

Author(s):

Frédéric Brocard ◽

Cédric Bardy ◽

Réjean Dubuc

Keyword(s):

Substance P ◽

Brain Stem ◽

Membrane Resistance ◽

Local Injections ◽

Current Threshold ◽

Firing Properties ◽

The Brain ◽

Spontaneous Postsynaptic Currents

Substance P initiates locomotion when injected in the brain stem of mammals. This study examined the possible role of this peptide on the supraspinal locomotor command system in lampreys. Substance P was bath applied or locally injected into an in vitro isolated brain stem, and the effects of the drug were examined on reticulospinal cells and on the occurrence of swimming in a semi-intact preparation. Bath applications of substance P induced sustained depolarizations occurring rhythmically in intracellularly recorded reticulospinal cells. Spiking activity was superimposed on the depolarizations and swimming was induced. The sustained depolarizations were abolished by tetrodotoxin, and substance P did not affect the membrane resistance of reticulospinal cells nor their firing properties, suggesting that it did not directly effect reticulospinal cells. To establish where the effects were exerted, successive lesions of the brain stem were made as well as local applications of the drug in the brain stem. Removing the mesencephalon abolished the sustained depolarizations, whereas large ejections of the drug in the mesencephalon excited reticulospinal cells and elicited bouts of swimming. More local injections into the mesencephalic locomotor region (MLR) also elicited swimming. After an injection of substance P, the current threshold needed to induce locomotion by MLR stimulation was decreased, and the size of the postsynaptic responses of reticulospinal cells to MLR stimulation was increased. Substance P also reduced the frequency of miniature spontaneous postsynaptic currents in reticulospinal cells. Taken together, these results suggest that substance P plays a neuromodulatory role on the brain stem locomotor networks of lampreys.

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Voltage-modulated membrane resistance in coupled leech neurons

Journal of Neurophysiology ◽

10.1152/jn.1979.42.2.465 ◽

1979 ◽

Vol 42 (2) ◽

pp. 465-475 ◽

Cited By ~ 9

Author(s):

B. Zipser

Keyword(s):

Membrane Resistance ◽

Resting Potential ◽

Reverse Direction ◽

Time Constants ◽

Voltage Dependent ◽

Current Threshold ◽

Coupling Factors ◽

The Impact ◽

Junctional Resistance ◽

Lateral Neurons

1. Resistive interactions have been studied between two pairs of large identifiable neurons in ganglion 6 of the leech CNS, called the lateral and rostral cells. Both are motor neurons causing penile eversion. 2. Lateral and rostral neurons have different membrane resistance properties. Input resistances of lateral neurons are virtually constant. By contrast, membrane resistances of rostral neurons are highly voltage dependent. When depolarized from resting potential to firing level, a rostral neuron's input resistance can increase 10-fold, from 30 to 300 Momega. 3. Voltage-dependent membrane characteristics of rostral neurons cause resistive interactions with lateral neurons to be nonlinear. DC potentials evoked in lateral cells are transmitted to rostral cells with an efficiency varying over a 10-fold range. Hyperpolarizing coupling is weak, with coupling factors of about 0.03. Depolarizing coupling factors increase progressively with increasing lateral neuron depolarization, reaching values of up to 0.3. 4. Membrane resistance changes in rostral neurons accompany lateral to rostral cell interactions. Input resistances increase during depolarizing and decrease during hyperpolarizing coupling potentials. The lateral to rostral cell junctional resistance is high and invariant, as evidenced by uniformly weak coupling in the reverse direction, from rostral to lateral neurons. 5. In conclusion, asymmetries in lateral to rostral cell interaction are based on postsynaptic rather than junctional resistance changes. The impact of the lateral onto the rostral cell's excitability contains a nonlinear component besides the usual linear additive one. As in conventional resistive coupling, depolarizing coupling potentials raise the rostral neuron closer to its voltage threshold. But more significantly, depolarizing coupling potentials lower the rostral neuron's current threshold because increases in resistance proportionately reduce the amount of excitatory current needed to reach firing level. Thus, the resistance change acts to amplify the input signal efficiency. In addition to the static changes in current threshold, the reostral neuron also changes dynamically. Membrane resistance increases lead to increases in space constant shrinking the neuron's electrical lenght. 6. Other properties of the network have been analyzed. The pair of lateral neurons is strongly coupled, whereas the pair of rostral neurons is weakly coupled, the coupling factors are 0.3 and 0.05, respectively. Hyperpolarizing membrane time constants for the lateral and rostral neurons are estimated to be between 100 and 200 ms. Time constants of depolarized rostral neurons are significantly larger.

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Miniaturization and Automation of a Human In Vitro Blood–Brain Barrier Model for the High-Throughput Screening of Compounds in the Early Stage of Drug Discovery

Pharmaceutics ◽

10.3390/pharmaceutics13060892 ◽

2021 ◽

Vol 13 (6) ◽

pp. 892

Author(s):

Elisa L. J. Moya ◽

Elodie Vandenhaute ◽

Eleonora Rizzi ◽

Marie-Christine Boucau ◽

Johan Hachani ◽

...

Keyword(s):

Drug Discovery ◽

Blood Brain Barrier ◽

Early Stage ◽

Molecular Transport ◽

Brain Barrier ◽

Blood Brain ◽

Cns Drugs ◽

The Impact ◽

The Brain

Central nervous system (CNS) diseases are one of the top causes of death worldwide. As there is a difficulty of drug penetration into the brain due to the blood–brain barrier (BBB), many CNS drugs treatments fail in clinical trials. Hence, there is a need to develop effective CNS drugs following strategies for delivery to the brain by better selecting them as early as possible during the drug discovery process. The use of in vitro BBB models has proved useful to evaluate the impact of drugs/compounds toxicity, BBB permeation rates and molecular transport mechanisms within the brain cells in academic research and early-stage drug discovery. However, these studies that require biological material (animal brain or human cells) are time-consuming and involve costly amounts of materials and plastic wastes due to the format of the models. Hence, to adapt to the high yields needed in early-stage drug discoveries for compound screenings, a patented well-established human in vitro BBB model was miniaturized and automated into a 96-well format. This replicate met all the BBB model reliability criteria to get predictive results, allowing a significant reduction in biological materials, waste and a higher screening capacity for being extensively used during early-stage drug discovery studies.

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The Impact of Bone on the Biology of Aging

Innovation in Aging ◽

10.1093/geroni/igaa057.2643 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 740-740

Author(s):

Gerard Karsenty

Keyword(s):

Muscle Function ◽

Male Fertility ◽

Leydig Cells ◽

Memory Loss ◽

Age Related ◽

Systematic Exploration ◽

Biology Of Aging ◽

The Impact ◽

The Brain ◽

Regulate Energy Metabolism

Abstract We hypothesized that bone may secrete hormones that regulate energy metabolism and reproduction. Testing this hypothesis revealed that the osteoblast-specific secreted protein osteocalcin is a hormone regulating glucose homeostasis and male fertility by signaling through a GPCR, Gprc6a, expressed in pancreatic β bells and Leydig cells of the testes. The systematic exploration of osteocalcin biology, revealed that it regulates an unexpectedly large spectrum of physiological functions in the brain and peripheral organs and that it has most features of an antigeromic molecule. As will be presented at the meeting, this body of work suggests that harnessing osteocalcin for therapeutic purposes may be beneficial in the treatment of age-related diseases such as depression, age-related memory loss and the decline in muscle function seen in sarcopenia.

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Crosstalk between Existential Phenomenological Psychotherapy and Neurological Sciences in Mood and Anxiety Disorders

Biomedicines ◽

10.3390/biomedicines9040340 ◽

2021 ◽

Vol 9 (4) ◽

pp. 340

Author(s):

Lehel Balogh ◽

Masaru Tanaka ◽

Nóra Török ◽

László Vécsei ◽

Shigeru Taguchi

Keyword(s):

Anxiety Disorders ◽

Biological Treatment ◽

Sense Of Self ◽

Phenomenological Approach ◽

Neurological Damage ◽

Mood And Anxiety Disorders ◽

New Interpretation ◽

And Behavior ◽

The Impact ◽

The Brain

Psychotherapy is a comprehensive biological treatment modifying complex underlying cognitive, emotional, behavioral, and regulatory responses in the brain, leading patients with mental illness to a new interpretation of the sense of self and others. Psychotherapy is an art of science integrated with psychology and/or philosophy. Neurological sciences study the neurological basis of cognition, memory, and behavior as well as the impact of neurological damage and disease on these functions, and their treatment. Both psychotherapy and neurological sciences deal with the brain; nevertheless, they continue to stay polarized. Existential phenomenological psychotherapy (EPP) has been in the forefront of meaning-centered counseling for almost a century. The phenomenological approach in psychotherapy originated in the works of Martin Heidegger, Ludwig Binswanger, Medard Boss, and Viktor Frankl, and it has been committed to accounting for the existential possibilities and limitations of one’s life. EPP provides philosophically rich interpretations and empowers counseling techniques to assist mentally suffering individuals by finding meaning and purpose to life. The approach has proven to be effective in treating mood and anxiety disorders. This narrative review article demonstrates the development of EPP, the therapeutic methodology, evidence-based accounts of its curative techniques, current understanding of mood and anxiety disorders in neurological sciences, and a possible converging path to translate and integrate meaning-centered psychotherapy and neuroscience, concluding that the EPP may potentially play a synergistic role with the currently prevailing medication-based approaches for the treatment of mood and anxiety disorders.

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Economic Analysis of a Transport Company in the Aspect of Car Vehicle Operation

Sustainability ◽

10.3390/su13010427 ◽

2021 ◽

Vol 13 (1) ◽

pp. 427

Author(s):

Magdalena Rykała ◽

Łukasz Rykała

Keyword(s):

Weather Conditions ◽

Neural Model ◽

Motor Vehicles ◽

Bulk Materials ◽

The Sustainable Development ◽

Average Temperature ◽

Transport Services ◽

Vehicle Operation ◽

The Impact

The article describes the issues of transport of bulk materials. The knowledge of this process has a key impact on the rational planning of transport tasks. It is necessary to have knowledge about the transport services market and the competition that exists in it. In order to achieve a competitive advantage on the market, enterprises should analyze data on the implementation of transport tasks on an ongoing basis. It is also important that the costs incurred from the conducted activity are minimized, while increasing the quality of services and taking into account the sustainable development of the enterprise. The study analyzes data from a few selected motor vehicles in the period of 3 years of operation, coming from an enterprise specializing in the transport of bulk materials. Moreover, a global sensitivity analysis was performed based on a neural model describing the impact of the analyzed factors on the company’s profit. The results show that the most important factors influencing the company’s profit are the fuel consumption of individual vehicles, the driver (driving style) and the month (average temperature, weather conditions).

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Agency, Responsibility, Selves, and the Mechanical Mind

Philosophies ◽

10.3390/philosophies6010007 ◽

2021 ◽

Vol 6 (1) ◽

pp. 7

Author(s):

Fiorella Battaglia

Keyword(s):

Philosophy Of Technology ◽

Extended Mind ◽

Human Machine Interaction ◽

Person Perspective ◽

Legal Perspective ◽

Area Of Concern ◽

Third Person Perspective ◽

The Mind ◽

The Impact ◽

The Brain

Moral issues arise not only when neural technology directly influences and affects people’s lives, but also when the impact of its interventions indirectly conceptualizes the mind in new, and unexpected ways. It is the case that theories of consciousness, theories of subjectivity, and third person perspective on the brain provide rival perspectives addressing the mind. Through a review of these three main approaches to the mind, and particularly as applied to an “extended mind”, the paper identifies a major area of transformation in philosophy of action, which is understood in terms of additional epistemic devices—including a legal perspective of regulating the human–machine interaction and a personality theory of the symbiotic connection between human and machine. I argue this is a new area of concern within philosophy, which will be characterized in terms of self-objectification, which becomes “alienation” following Ernst Kapp’s philosophy of technology. The paper argues that intervening in the brain can affect how we conceptualize the mind and modify its predicaments.

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Developmental cannabidiol exposure increases anxiety and modifies genome-wide brain DNA methylation in adult female mice

Clinical Epigenetics ◽

10.1186/s13148-020-00993-4 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Nicole M. Wanner ◽

Mathia Colwell ◽

Chelsea Drown ◽

Christopher Faulk

Keyword(s):

Dna Methylation ◽

Molecular Mechanisms ◽

Coat Color ◽

Brain Regions ◽

Functional Enrichment ◽

Positive Effects ◽

Genome Wide ◽

Nulliparous Female ◽

The Impact ◽

The Brain

Abstract Background Use of cannabidiol (CBD), the primary non-psychoactive compound found in cannabis, has recently risen dramatically, while relatively little is known about the underlying molecular mechanisms of its effects. Previous work indicates that direct CBD exposure strongly impacts the brain, with anxiolytic, antidepressant, antipsychotic, and other effects being observed in animal and human studies. The epigenome, particularly DNA methylation, is responsive to environmental input and can direct persistent patterns of gene regulation impacting phenotype. Epigenetic perturbation is particularly impactful during embryogenesis, when exogenous exposures can disrupt critical resetting of epigenetic marks and impart phenotypic effects lasting into adulthood. The impact of prenatal CBD exposure has not been evaluated; however, studies using the psychomimetic cannabinoid Δ9-tetrahydrocannabinol (THC) have identified detrimental effects on psychological outcomes in developmentally exposed adult offspring. We hypothesized that developmental CBD exposure would have similar negative effects on behavior mediated in part by the epigenome. Nulliparous female wild-type Agouti viable yellow (Avy) mice were exposed to 20 mg/kg CBD or vehicle daily from two weeks prior to mating through gestation and lactation. Coat color shifts, a readout of DNA methylation at the Agouti locus in this strain, were measured in F1 Avy/a offspring. Young adult F1 a/a offspring were then subjected to tests of working spatial memory and anxiety/compulsive behavior. Reduced-representation bisulfite sequencing was performed on both F0 and F1 cerebral cortex and F1 hippocampus to identify genome-wide changes in DNA methylation for direct and developmental exposure, respectively. Results F1 offspring exposed to CBD during development exhibited increased anxiety and improved memory behavior in a sex-specific manner. Further, while no significant coat color shift was observed in Avy/a offspring, thousands of differentially methylated loci (DMLs) were identified in both brain regions with functional enrichment for neurogenesis, substance use phenotypes, and other psychologically relevant terms. Conclusions These findings demonstrate for the first time that despite positive effects of direct exposure, developmental CBD is associated with mixed behavioral outcomes and perturbation of the brain epigenome.

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Preserving Integrity in the Face of Performance Threat

Psychological Science ◽

10.1177/0956797612448483 ◽

2012 ◽

Vol 23 (12) ◽

pp. 1455-1460 ◽

Cited By ~ 23

Author(s):

Lisa Legault ◽

Timour Al-Khindi ◽

Michael Inzlicht

Keyword(s):

Error Detection ◽

Error Monitoring ◽

Error Related Negativity ◽

Threatening Information ◽

Electrophysiological Responses ◽

The Face ◽

And Performance ◽

The Impact ◽

The Brain

Self-affirmation produces large effects: Even a simple reminder of one’s core values reduces defensiveness against threatening information. But how, exactly, does self-affirmation work? We explored this question by examining the impact of self-affirmation on neurophysiological responses to threatening events. We hypothesized that because self-affirmation increases openness to threat and enhances approachability of unfavorable feedback, it should augment attention and emotional receptivity to performance errors. We further hypothesized that this augmentation could be assessed directly, at the level of the brain. We measured self-affirmed and nonaffirmed participants’ electrophysiological responses to making errors on a task. As we anticipated, self-affirmation elicited greater error responsiveness than did nonaffirmation, as indexed by the error-related negativity, a neural signal of error monitoring. Self-affirmed participants also performed better on the task than did nonaffirmed participants. We offer novel brain evidence that self-affirmation increases openness to threat and discuss the role of error detection in the link between self-affirmation and performance.

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