scholarly journals A multi-scale model reveals cellular and physiological mechanisms underlying hyperpolarisation-gated synaptic plasticity

2018 ◽  
Author(s):  
Yubin Xie ◽  
Marcel Kazmierczyk ◽  
Bruce P. Graham ◽  
Mayank B. Dutia ◽  
Melanie I. Stefan ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Nerve Stimulation ◽  
Vestibular Nerve ◽  
Biochemical Reaction ◽  
Medial Vestibular Nucleus ◽  
Scale Model ◽  
Reaction Systems ◽  
Multi Scale ◽  
Wide Range

AbstractNeurons in the medial vestibular nucleus (MVN) display hyperpolarisation-gated synaptic plasticity, where inhibition believed to come from cerebellar cortical Purkinje cells can induce long-term potentiation (LTP) or long-term depression (LTD) of vestibular nerve afferent synapses. This phenomenon is thought to underlie the plasticity of the vestibulo-ocular reflex (VOR). The molecular and cellular mechanisms involved are largely unknown. Here we present a novel multi-scale computational model, which captures both electrophysiological and biochemical signalling at vestibular nerve synapses on proximal dendrites of the MVN neuron. We show that AMPA receptor phosphorylation at the vestibular synapse depends in complex ways on dendritic calcium influx, which is in turn shaped by patterns of post-synaptic hyperpolarisation and vestibular nerve stimulation. Hyperpolarisation-gated synaptic plasticity critically depends on the activation of LVA calcium channels and on the interplay between CaMKII and PP2B in dendrites of the post-synaptic MVN cell. The extent and direction of synaptic plasticity depend on the strength and duration of hyperpolarisation, and on the relative timing of hyperpolarisation and vestibular nerve stimulation. The multi-scale model thus enables us to explore in detail the interactions between electrophysiological activation and post-synaptic biochemical reaction systems. More generally, this model has the potential to address a wide range of questions about neural signal integration, post-synaptic biochemical reaction systems and plasticity.

scholarly journals Multi‐scale approach for simulating time‐delay biochemical reaction systems

2015 ◽  
Vol 9 (1) ◽  
pp. 31-38 ◽  
Author(s):  
Yuanling Niu ◽  
Kevin Burrage ◽  
Chengjian Zhang
Keyword(s):  
Time Delay ◽  
Biochemical Reaction ◽  
Reaction Systems ◽  
Multi Scale

scholarly journals Vagus Nerve Stimulation Enhances Extinction of Conditioned Fear in Rats and Modulates Arc Protein, CaMKII, and GluN2B-Containing NMDA Receptors in the Basolateral Amygdala

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Amanda C. Alvarez-Dieppa ◽  
Kimberly Griffin ◽  
Sheridan Cavalier ◽  
Christa K. McIntyre
Keyword(s):  
Synaptic Plasticity ◽  
Vagus Nerve ◽  
Nmda Receptors ◽  
Fear Conditioning ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Basolateral Amygdala ◽  
Conditioned Fear ◽  
Associated Proteins

Vagus nerve stimulation (VNS) enhances the consolidation of extinction of conditioned fear. High frequency stimulation of the infralimbic cortex (IL) produces long-term potentiation in the basolateral amygdala (BLA) in rats given VNS-paired extinction training, whereas the same stimulation produces long-term depression in sham-treated rats. The present study investigated the state of synaptic plasticity-associated proteins in the BLA that could be responsible for this shift. Male Sprague-Dawley rats were separated into 4 groups: auditory fear conditioning only (fear-conditioned); fear conditioning + 20 extinction trials (extended-extinction); fear conditioning + 4 extinction trials paired with sham stimulation (sham-extinction); fear conditioning + 4 extinction trials paired with VNS (VNS-extinction). Freezing was significantly reduced in extended-extinction and VNS-extinction rats. Western blots were used to quantify expression and phosphorylation state of synaptic plasticity-associated proteins such as Arc, CaMKII, ERK, PKA, and AMPA and NMDA receptors. Results show significant increases in GluN2B expression and phosphorylated CaMKII in BLA samples from VNS- and extended-extinction rats. Arc expression was significantly reduced in VNS-extinction rats compared to all groups. Administration of the GluN2B antagonist ifenprodil immediately after fear extinction training blocked consolidation of extinction learning. Results indicate a role for BLA CaMKII-induced GluN2B expression and reduced Arc protein in VNS-enhanced extinction.

scholarly journals An implant for long-term cervical vagus nerve stimulation in mice

2020 ◽  
Author(s):  
Ibrahim T. Mughrabi ◽  
Jordan Hickman ◽  
Naveen Jayaprakash ◽  
Eleni S. Papadoyannis ◽  
Adam Abbas ◽  
...  
Keyword(s):  
Heart Rate ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Therapeutic Potential ◽  
Therapeutic Implications ◽  
Wide Range ◽  
Heart Rate Threshold

AbstractVagus nerve stimulation (VNS) is a neuromodulation therapy with the potential to treat a wide range of chronic conditions in which inflammation is implicated, including type 2 diabetes, obesity, atherosclerosis and heart failure. Many of these diseases have well-established mouse models but due to the significant surgical and engineering challenges that accompany a reliable interface for long-term VNS in mice, the therapeutic implications of this bioelectronic approach remain unexplored. Here, we describe a long-term VNS implant in mice, developed at 3 research laboratories and validated for between-lab reproducibility. Implant functionality was evaluated over 3-8 weeks in 81 anesthetized or conscious mice by determining the stimulus intensity required to elicit a change in heart rate (heart rate threshold, HRT). HRT was also used as a method to standardize stimulation dosing across animals. Overall, 60-90% of implants produced stimulus-evoked physiological responses for at least 4 weeks, with HRT values stabilizing after the second week of implantation. Furthermore, stimulation delivered through 6-week-old implants decreased TNF levels in a subset of mice with acute inflammation caused by endotoxemia. Histological examination of 4- to 6-week-old implants revealed fibrotic encapsulation and no gross fiber loss. This implantation and dosing approach provide a tool to systematically investigate the therapeutic potential of long-term VNS in chronic diseases modeled in the mouse, the most widely used vertebrate species in biomedical research.

Emergence of Action Potential Generation and Synaptic Transmission in Vestibular Nucleus Neurons

2006 ◽  
Vol 96 (3) ◽  
pp. 1215-1226 ◽  
Author(s):  
Mei Shao ◽  
June C. Hirsch ◽  
Kenna D. Peusner
Keyword(s):  
Nerve Stimulation ◽  
Vestibular Nucleus ◽  
Vestibular Nerve ◽  
Action Potential Generation ◽  
Potential Generation ◽  
Low Frequencies ◽  
Excitatory Postsynaptic Currents ◽  
Principal Cells ◽  
Functional Development

Principal cells of the chick tangential nucleus are vestibular nucleus neurons in the hindbrain. Although detailed information is available on the morphogenesis of principal cells and synaptogenesis of primary vestibular fibers, this is the first study of their early functional development, when vestibular terminals emerge at embryonic days 10 and 13 (E10 and E13). At E10, 60% of principal cells generated spikes on depolarization, whereas 50% exhibited excitatory postsynaptic currents (EPSCs) on vestibular-nerve stimulation. The frequency was 0.2 Hz for glutamatergic spontaneous EPSCs (sEPSCs) at −60 mV, and 0.6 Hz for spontaneous inhibitory postsynaptic current (sIPSC) at +10 mV and completely GABAergic. All of these synaptic events were TTX-insensitive, miniature events. At E13, 50% of principal cells generated spikes on depolarization and 82% exhibited EPSCs on vestibular-nerve stimulation. The frequency was 0.7 Hz for sEPSCs at −60 mV, and 0.8 Hz for sIPSCs at +10 mV. Most principal cells had sIPSCs composed of both GABAergic (75%) and glycinergic (25%) events, but a few cells had only GABAergic sIPSCs. TTX decreased the frequency of EPSCs by 12%, and the IPSCs by 17%. In summary, at E10, some principal cells generated immature spikes on depolarization and EPSCs on vestibular-nerve stimulation. At E10, GABAergic events predominated, AMPA events had low frequencies, and glycinergic activity was absent. By E13, glycinergic events first appeared. This data were compared systematically to that obtained from the late-term embryo and hatchling to reveal the long-term sequence of changes in synaptic events and excitability and offer a broader understanding of how the vestibular system is assembled during development.

Simulating the Emptying of a Water Bottle With a Multi-Scale Two-Fluid Approach

2018 ◽  
Author(s):  
Samuel Mer ◽  
Olivier Praud ◽  
Jacques Magnaudet ◽  
Véronique Roig
Keyword(s):  
Bubble Formation ◽  
Computational Cost ◽  
Scale Model ◽  
Water Bottle ◽  
Local Flow ◽  
Spatial And Temporal Scales ◽  
Multi Scale ◽  
Wide Range ◽  
Bottle Neck ◽  
Liquid Flows

Multiple industrial processes involve gas-liquid flows characterized by a wide range of spatial and temporal scales. Simulating such flows remains a major challenge nowadays, as the computational cost associated with Direct Numerical Simulation still makes it unaffordable. For such configurations, an interesting alternative to DNS is the use of multi-scale approaches. In the latter, large enough bubbles are fully resolved and may deform over time, while smaller bubbles are modeled as a dispersed phase using subgrid scale models. The interfacial momentum transfer terms are then tailored to the local flow configuration. The closure models still involved in these approaches and the influence of the cut-off length separating the resolved and modeled bubbles definitely need to be validated against detailed experiments. In order to assess the validity of these models, we present a one-to-one comparison between experiments performed in a simple configuration, namely the emptying of a water bottle, and numerical simulations using the aforementioned approach. The results are found to reliably reproduce the genesis of the oscillation mechanism, which is governed by the bubble formation at the bottle neck. The multi-scale model also qualitatively reproduces the fragmentation process of large bubbles during their rise in the water column. However local experimental data are required to assess more quantitatively these results.

Antigen-induced long-term potentiation of nicotinic synaptic transmission in the superior cervical ganglion of the guinea pig

1995 ◽  
Vol 73 (5) ◽  
pp. 2004-2016 ◽  
Author(s):  
D. Weinreich ◽  
B. J. Undem ◽  
G. Taylor ◽  
M. F. Barry
Keyword(s):  
Synaptic Plasticity ◽  
Guinea Pig ◽  
Synaptic Transmission ◽  
Specific Antigen ◽  
Long Term Potentiation ◽  
Antigen Challenge ◽  
Lipoxygenase Inhibitors ◽  
Term Potentiation ◽  
Wide Range

1. Recordings of evoked postganglionic compound action potentials (CAPs) evoked by preganglionic stimulation were obtained from guinea pig superior cervical ganglia (SCGs) in vitro to study the effects of specific antigen challenge on ganglionic synaptic transmission. SCGs were removed from guinea pigs actively sensitized to ovalbumin. 2. Exposing SCGs from sensitized animals to the sensitizing antigen (0.01-10 micrograms/ml) for 5 min produced a sustained increase in the magnitude of the evoked CAP unaccompanied by a change in the preganglionic volley. Nonsensitizing antigens were ineffective. Also ineffective were antigens applied to nonsensitized SCG. This persistent antigen-induced increase in synaptic transmission was designated antigen-induced long-term potentiation (LTP) (A-LTP) because its duration (> 30 min) greatly outlasted posttetanic potentiation (PTP) in this ganglion. 3. A-LTP and neurogenic LTP (N-LTP) were observed to coexist in the same ganglion; the presence of one form of synaptic plasticity did not preclude the development of the other. Both phenomena were influenced by presynaptic factors: prolonged (2 h, 40 Hz) repetitive presynaptic stimulation abolished A-LTP or N-LTP but did not affect PTP. 4. By contrast to N-LTP, which requires a brief presynaptic tetanus, A-LTP could be triggered over a wide range of presynaptic stimulation (0.016-3 Hz) or even in the absence of presynaptic stimulation. 5. The amplitude and duration of A-LTP were not significantly affected by 1) H1, H2, or H3 histamine receptor antagonists added before or after antigen challenge; 2) the presence of saturating concentrations of histamine (100-300 microM); 3) the presence of specific or nonspecific lipoxygenase inhibitors or a selective cyclooxygenase inhibitor; or 4) blockade of alpha- or beta-adrenergic receptors, 5-HT3 receptors, muscarinic receptors, or glutamate receptors, or inhibition of acetylcholinesterase or protein synthesis. 6. Our results indicate that specific antigen challenge of isolated sympathetic ganglia activates resident mast cells to release substances that initiate a novel form of synaptic plasticity, an activity-independent and long-lasting increase in synaptic efficacy.

scholarly journals MULTI-SCALE MODEL ELABORATION FOR CREDITWORTHINESS DIAGNOSTICS OF EXPORT PRODUCTION ENTERPRISES OF THE AGRICULTURAL TRADE MARKET

2019 ◽  
Vol 6 ◽  
pp. 19-30
Author(s):  
Olena Sergienko ◽  
Olena Shapran ◽  
Oleksandr Bilotserkivskyi ◽  
Iryna Alieksieieva
Keyword(s):  
Evaluation System ◽  
Agricultural Trade ◽  
Economic Indicators ◽  
Scale Model ◽  
Decision Making Process ◽  
One Dimensional ◽  
Multi Scale ◽  
Wide Range ◽  
Trade Market

The methodology for the agrarian enterprises’ creditworthiness diagnostic has been developed and implemented, and has allowed to solve the following objectives: conducting of observations and evaluating of financially-economic indicators, classification of enterprises by the level of creditworthiness, distinction and identification enterprises according to the level of creditworthiness and assessing the differences between classes by creditworthiness, with taking into account the sizes of enterprises. Based on the use of the complex of multidimensional analytical methods, the differences are defined under either one-dimensional evaluation system (by creditworthiness and size) or a two-level assessment of the joint cross impact of factors on creditworthiness. The proposed four-step technology for diagnosing of the agrarian enterprises creditworthiness substantially expands the components of the creditworthiness level evaluation of enterprises and, as a consequence, improves the timeliness of decision-making process about identifying and locating of weaknesses and "bottlenecks". The coverage of a sufficient number of financial and economic indicators and the implementation of a wide range of methods and models enable to fully evaluate and analyze the existing state of creditworthiness with a view to improve and establish the effective functioning of the enterprise as a whole.

Floccular Modulation of Vestibuloocular Pathways and Cerebellum-Related Plasticity: An In Vitro Whole Brain Study

2000 ◽  
Vol 84 (5) ◽  
pp. 2514-2528 ◽  
Author(s):  
Alexander L. Babalian ◽  
Pierre-Paul Vidal
Keyword(s):  
Purkinje Cells ◽  
Nerve Stimulation ◽  
Inferior Olive ◽  
Vestibular Nuclei ◽  
Vestibular Nerve ◽  
Abducens Nucleus ◽  
Postsynaptic Potentials ◽  
Oculomotor Nerves ◽  
Stimulation Of

The isolated whole brain (IWB) preparation of the guinea pig was used to investigate the floccular modulation of vestibular-evoked responses in abducens and oculomotor nerves and abducens nucleus; for identification of flocculus target neurons (FTNs) in the vestibular nuclei and intracellular study of some of their physiological properties; to search for possible flocculus-dependent plasticity at the FTN level by pairing of vestibular nerve and floccular stimulations; and to study the possibility of induction of long-term depression (LTD) in Purkinje cells by paired stimulation of the inferior olive and vestibular nerve. Stimulation of the flocculus had only effects on responses evoked from the ipsilateral (with respect to the stimulated flocculus) vestibular nerve. Floccular stimulation significantly inhibited the vestibular-evoked discharges in oculomotor nerves on both sides and the inhibitory field potential in the ipsilateral abducens nucleus while the excitatory responses in the contralateral abducens nerve and nucleus were free from such inhibition. Eleven second-order vestibular neurons were found to receive a short-latency monosynaptic inhibitory input from the flocculus and were thus characterized as FTNs. Monosynaptic inhibitory postsynaptic potentials from the flocculus were bicuculline sensitive, suggesting a GABAA-ergic transmission from Purkinje cells to FTNs. Two of recorded FTNs could be identified as vestibulospinal neurons by their antidromic activation from the cervical segments of the spinal cord. Several pairing paradigms were investigated in which stimulation of the flocculus could precede, coincide with, or follow the vestibular nerve stimulation. None of them led to long-term modification of responses in the abducens nucleus or oculomotor nerve evoked by activation of vestibular afferents. On the other hand, pairing of the inferior olive and vestibular nerve stimulation resulted in approximately a 30% reduction of excitatory postsynaptic potentials evoked in Purkinje cells by the vestibular nerve stimulation. This reduction was pairing-specific and lasted throughout the entire recording time of the neurons. Thus in the IWB preparation, we were able to induce a LTD in Purkinje cells, but we failed to detect traces of flocculus-dependent plasticity at the level of FTNs in vestibular nuclei. Although these data cannot rule out the possibility of synaptic modifications in FTNs and/or at other brain stem sites under different experimental conditions, they are in favor of the hypothesis that the LTD in the flocculus could be the essential mechanism of cellular plasticity in the vestibuloocular pathways.

Multi-Scale Finite Element Modeling of Alumina Ceramics Undergoing Laser-Assisted Machining

2014 ◽  
Author(s):  
Xiangyang Dong ◽  
Yung C. Shin
Keyword(s):  
Finite Element ◽  
High Temperatures ◽  
Cutting Forces ◽  
Scale Model ◽  
Zone Model ◽  
Alumina Ceramics ◽  
Weight Percentage ◽  
Laser Assisted Machining ◽  
Multi Scale ◽  
Wide Range

Alumina ceramics, due to their excellent properties of high hardness, corrosion resistance and low thermal expansion coefficient, are important industrial materials with a wide range of applications, but these materials also present difficulty in machining with low material removal rates and high tool wear. This study is concerned with laser-assisted machining (LAM) of high weight percentage of alumina ceramics to improve the machinability by a single point cutting tool while reducing the cutting forces. A multi-scale model is developed for simulating the machining of alumina ceramics. In the polycrystalline form, the properties of alumina ceramics are strongly related to the glass interface existing in their microstructure, particularly at high temperatures. The interface is characterized by a cohesive zone model (CZM) with the traction-separation law while the alumina grains are modeled as continuum elements with isotropic properties separated by the interface. Bulk deformation and brittle failure are considered for the alumina grains. Molecular dynamics (MD) simulations are carried out to obtain the atomistic structures and parameterize traction-separation laws for the interfaces of different compositions of alumina ceramics at high temperatures. The generated parameterized traction-separation laws are then incorporated into a finite element model in Abaqus to simulate the intergranular cracks. For validation purposes, simulated results of the multi-scale approach are compared with the experimental measurements of the cutting forces. The model is successful in predicting cutting forces with respect to the different weight percentage and composition of alumina ceramics at high temperatures in LAM processes.

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