Ephaptic Coupling in Hybrid Neuronal Model

Author(s):  
Gabriel Moreno Cunha ◽  
Gilberto Corso ◽  
José Garcia Vivas Miranda ◽  
Gustavo Zampier Dos Santos Lima

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.

2018 ◽  
Author(s):  
Maria Teleńczuk ◽  
Romain Brette ◽  
Alain Destexhe ◽  
Bartosz Teleńczuk

AbstractAction potentials (APs) are electric phenomena that are recorded both intracellularly and extracellularly. APs are usually initiated in the short segment of the axon called the axon initial segment (AIS). It was recently proposed that at onset of an AP the soma and the AIS form a dipole. We study the extracellular signature (the extracellular action potential, EAP) generated by such a dipole. First, we demonstrate the formation of the dipole and its extracellular signature in detailed morphological models of a reconstructed pyramidal neuron. Then, we study the EAP waveform and its spatial dependence in models with axonal AP initiation and contrast it with the EAP obtained in models with somatic AP initiation. We show that in the models with axonal AP initiation the dipole forms between somatodendritic compartments and the AIS, and not between soma and dendrites as in the classical models. Soma-dendrites dipole is present only in models with somatic AP initiation. Our study has consequences for interpreting extracellular recordings of single-neuron activity and determining electrophysiological neuron types, but also for better understanding the origins of the high-frequency macroscopic electric fields recorded in the brain.New & NoteworthyWe studied the consequences of the action potential (AP) initiation site on the extracellular signatures of APs. We show that: (1) at the time of AP initiation the action initial segment (AIS) forms a dipole with the soma, (2) the width but not (3) amplitude of the extracellular AP generated by this dipole increases with the soma-AIS distance. This may help to monitor dynamic changes in the AIS position in experimental in vivo recordings.


2021 ◽  
Vol 20 ◽  
pp. 196-202
Author(s):  
Shima Pilehvari ◽  
Lei Zhang ◽  
Rene V. Mayorga

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.


2019 ◽  
Vol 19 (4) ◽  
pp. 857-873
Author(s):  
Karol Borzuta ◽  
Dariusz Lisiak ◽  
Piotr Janiszewski ◽  
Eugenia Grześkowiak

AbstractThe aim of the paper was a review of the scientific achievements in physiological stunning and slaughtering mechanisms, control methods of consciousness and their effect on meat quality. Special attention was paid to neurophysiological phenomena that accompany the process of depriving consciousness before animal deaths using mechanical, electrical and gas stunning methods. These mechanisms are associated with cerebral hypoxia or ischemia or depolarization, acidification and the destruction of cerebral neurons. Such effects can be caused by shock waves, bleeding, electric fields, reduction or arrest of the circulation of blood in the brain, high CO2 level or low O2 level in inhaled air or by the mechanical damage of neurons. Some of the stunning methods cause immediate and some gradual consciousness loss. An important factor in the animals’ slaughtering process is the estimation of their consciousness level before bleeding. The indicators of consciousness during mechanical, electrical and gas stunning are discussed within this paper. It is pointed out that at least 2 indicators should be used when estimating animals’ consciousness after stunning, e.g. phonic and clonic limb movements and lack of breathing. Ten indicators to control the consciousness were described. The effect of stunning on meat quality is also discussed. It was found that the impact of this process on the quality is not clear. However, the prevailing view is that electric stunning causes effusions and blood haemorrhages in meat. Whereas gas stunning with a CO2 mixture diminishes the risk of PSE meat. Despite numerous scientific research on the slaughter process there is still deficiency in knowledge on losing consciousness mechanisms and feeling pain. It might be useful to extend the knowledge concerning neurotransmitters and use of magnetic resonance in future studies.


2021 ◽  
Vol 22 (13) ◽  
pp. 7051
Author(s):  
Vitalii Kim ◽  
Emily Gudvangen ◽  
Oleg Kondratiev ◽  
Luis Redondo ◽  
Shu Xiao ◽  
...  

Intense pulsed electric fields (PEF) are a novel modality for the efficient and targeted ablation of tumors by electroporation. The major adverse side effects of PEF therapies are strong involuntary muscle contractions and pain. Nanosecond-range PEF (nsPEF) are less efficient at neurostimulation and can be employed to minimize such side effects. We quantified the impact of the electrode configuration, PEF strength (up to 20 kV/cm), repetition rate (up to 3 MHz), bi- and triphasic pulse shapes, and pulse duration (down to 10 ns) on eliciting compound action potentials (CAPs) in nerve fibers. The excitation thresholds for single unipolar but not bipolar stimuli followed the classic strength–duration dependence. The addition of the opposite polarity phase for nsPEF increased the excitation threshold, with symmetrical bipolar nsPEF being the least efficient. Stimulation by nsPEF bursts decreased the excitation threshold as a power function above a critical duty cycle of 0.1%. The threshold reduction was much weaker for symmetrical bipolar nsPEF. Supramaximal stimulation by high-rate nsPEF bursts elicited only a single CAP as long as the burst duration did not exceed the nerve refractory period. Such brief bursts of bipolar nsPEF could be the best choice to minimize neuromuscular stimulation in ablation therapies.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Martin L. Pall

Abstract Millimeter wave (MM-wave) electromagnetic fields (EMFs) are predicted to not produce penetrating effects in the body. The electric but not magnetic part of MM-EMFs are almost completely absorbed within the outer 1 mm of the body. Rodents are reported to have penetrating MM-wave impacts on the brain, the myocardium, liver, kidney and bone marrow. MM-waves produce electromagnetic sensitivity-like changes in rodent, frog and skate tissues. In humans, MM-waves have penetrating effects including impacts on the brain, producing EEG changes and other neurological/neuropsychiatric changes, increases in apparent electromagnetic hypersensitivity and produce changes on ulcers and cardiac activity. This review focuses on several issues required to understand penetrating effects of MM-waves and microwaves: 1. Electronically generated EMFs are coherent, producing much higher electrical and magnetic forces then do natural incoherent EMFs. 2. The fixed relationship between electrical and magnetic fields found in EMFs in a vacuum or highly permeable medium such as air, predicted by Maxwell’s equations, breaks down in other materials. Specifically, MM-wave electrical fields are almost completely absorbed in the outer 1 mm of the body due to the high dielectric constant of biological aqueous phases. However, the magnetic fields are very highly penetrating. 3. Time-varying magnetic fields have central roles in producing highly penetrating effects. The primary mechanism of EMF action is voltage-gated calcium channel (VGCC) activation with the EMFs acting via their forces on the voltage sensor, rather than by depolarization of the plasma membrane. Two distinct mechanisms, an indirect and a direct mechanism, are consistent with and predicted by the physics, to explain penetrating MM-wave VGCC activation via the voltage sensor. Time-varying coherent magnetic fields, as predicted by the Maxwell–Faraday version of Faraday’s law of induction, can put forces on ions dissolved in aqueous phases deep within the body, regenerating coherent electric fields which activate the VGCC voltage sensor. In addition, time-varying magnetic fields can directly put forces on the 20 charges in the VGCC voltage sensor. There are three very important findings here which are rarely recognized in the EMF scientific literature: coherence of electronically generated EMFs; the key role of time-varying magnetic fields in generating highly penetrating effects; the key role of both modulating and pure EMF pulses in greatly increasing very short term high level time-variation of magnetic and electric fields. It is probable that genuine safety guidelines must keep nanosecond timescale-variation of coherent electric and magnetic fields below some maximum level in order to produce genuine safety. These findings have important implications with regard to 5G radiation.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 892
Author(s):  
Elisa L. J. Moya ◽  
Elodie Vandenhaute ◽  
Eleonora Rizzi ◽  
Marie-Christine Boucau ◽  
Johan Hachani ◽  
...  

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.


2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 740-740
Author(s):  
Gerard Karsenty

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.


Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 340
Author(s):  
Lehel Balogh ◽  
Masaru Tanaka ◽  
Nóra Török ◽  
László Vécsei ◽  
Shigeru Taguchi

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.


Philosophies ◽  
2021 ◽  
Vol 6 (1) ◽  
pp. 7
Author(s):  
Fiorella Battaglia

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.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Nicole M. Wanner ◽  
Mathia Colwell ◽  
Chelsea Drown ◽  
Christopher Faulk

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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