186 research outputs found
A Mathematical model for Astrocytes mediated LTP at Single Hippocampal Synapses
Many contemporary studies have shown that astrocytes play a significant role
in modulating both short and long form of synaptic plasticity. There are very
few experimental models which elucidate the role of astrocyte over Long-term
Potentiation (LTP). Recently, Perea & Araque (2007) demonstrated a role of
astrocytes in induction of LTP at single hippocampal synapses. They suggested a
purely pre-synaptic basis for induction of this N-methyl-D- Aspartate (NMDA)
Receptor-independent LTP. Also, the mechanisms underlying this pre-synaptic
induction were not investigated. Here, in this article, we propose a
mathematical model for astrocyte modulated LTP which successfully emulates the
experimental findings of Perea & Araque (2007). Our study suggests the role of
retrograde messengers, possibly Nitric Oxide (NO), for this pre-synaptically
modulated LTP.Comment: 51 pages, 15 figures, Journal of Computational Neuroscience (to
appear
Gap Junctions and Epileptic Seizures – Two Sides of the Same Coin?
Electrical synapses (gap junctions) play a pivotal role in the synchronization of
neuronal ensembles which also makes them likely agonists of pathological brain
activity. Although large body of experimental data and theoretical
considerations indicate that coupling neurons by electrical synapses promotes
synchronous activity (and thus is potentially epileptogenic), some recent
evidence questions the hypothesis of gap junctions being among purely
epileptogenic factors. In particular, an expression of inter-neuronal gap
junctions is often found to be higher after the experimentally induced seizures
than before. Here we used a computational modeling approach to address the role
of neuronal gap junctions in shaping the stability of a network to perturbations
that are often associated with the onset of epileptic seizures. We show that
under some circumstances, the addition of gap junctions can increase the
dynamical stability of a network and thus suppress the collective electrical
activity associated with seizures. This implies that the experimentally observed
post-seizure additions of gap junctions could serve to prevent further
escalations, suggesting furthermore that they are a consequence of an adaptive
response of the neuronal network to the pathological activity. However, if the
seizures are strong and persistent, our model predicts the existence of a
critical tipping point after which additional gap junctions no longer suppress
but strongly facilitate the escalation of epileptic seizures. Our results thus
reveal a complex role of electrical coupling in relation to epileptiform events.
Which dynamic scenario (seizure suppression or seizure escalation) is ultimately
adopted by the network depends critically on the strength and duration of
seizures, in turn emphasizing the importance of temporal and causal aspects when
linking gap junctions with epilepsy
Scaling Effects and Spatio-Temporal Multilevel Dynamics in Epileptic Seizures
Epileptic seizures are one of the most well-known dysfunctions of the nervous system. During a seizure, a highly synchronized behavior of neural activity is observed that can cause symptoms ranging from mild sensual malfunctions to the complete loss of body control. In this paper, we aim to contribute towards a better understanding of the dynamical systems phenomena that cause seizures. Based on data analysis and modelling, seizure dynamics can be identified to possess multiple spatial scales and on each spatial scale also multiple time scales. At each scale, we reach several novel insights. On the smallest spatial scale we consider single model neurons and investigate early-warning signs of spiking. This introduces the theory of critical transitions to excitable systems. For clusters of neurons (or neuronal regions) we use patient data and find oscillatory behavior and new scaling laws near the seizure onset. These scalings lead to substantiate the conjecture obtained from mean-field models that a Hopf bifurcation could be involved near seizure onset. On the largest spatial scale we introduce a measure based on phase-locking intervals and wavelets into seizure modelling. It is used to resolve synchronization between different regions in the brain and identifies time-shifted scaling laws at different wavelet scales. We also compare our wavelet-based multiscale approach with maximum linear cross-correlation and mean-phase coherence measures
Nonlinear gap junctions enable long-distance propagation of pulsating calcium waves in astrocyte networks
A new paradigm has recently emerged in brain science whereby communications
between glial cells and neuron-glia interactions should be considered together
with neurons and their networks to understand higher brain functions. In
particular, astrocytes, the main type of glial cells in the cortex, have been
shown to communicate with neurons and with each other. They are thought to form
a gap-junction-coupled syncytium supporting cell-cell communication via
propagating Ca2+ waves. An identified mode of propagation is based on
cytoplasm-to-cytoplasm transport of inositol trisphosphate (IP3) through gap
junctions that locally trigger Ca2+ pulses via IP3-dependent Ca2+-induced Ca2+
release. It is, however, currently unknown whether this intracellular route is
able to support the propagation of long-distance regenerative Ca2+ waves or is
restricted to short-distance signaling. Furthermore, the influence of the
intracellular signaling dynamics on intercellular propagation remains to be
understood. In this work, we propose a model of the gap-junctional route for
intercellular Ca2+ wave propagation in astrocytes showing that: (1)
long-distance regenerative signaling requires nonlinear coupling in the gap
junctions, and (2) even with nonlinear gap junctions, long-distance
regenerative signaling is favored when the internal Ca2+ dynamics implements
frequency modulation-encoding oscillations with pulsating dynamics, while
amplitude modulation-encoding dynamics tends to restrict the propagation range.
As a result, spatially heterogeneous molecular properties and/or weak couplings
are shown to give rise to rich spatiotemporal dynamics that support complex
propagation behaviors. These results shed new light on the mechanisms
implicated in the propagation of Ca2+ waves across astrocytes and precise the
conditions under which glial cells may participate in information processing in
the brain.Comment: Article: 30 pages, 7 figures. Supplementary Material: 11 pages, 6
figure
Intramolecular hydrogen transfer reactions of thiyl radicals from glutathione: formation of carbon-centered radical at Glu, Cys and Gly
This document is the Accepted Manuscript version of a Published Work that appeared in final form in
Chemical Research in Toxicology, copyright © American Chemical Society after peer review and technical editing by the publisher.
To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/tx3000494Glutathione thiyl radicals (GS•) were generated in H2O and D2O by either exposure of GSH to AAPH#, photoirradiation of GSH in the presence of acetone, or photoirradiation of GSSG. Detailed interpretation of the fragmentation pathways of deuterated GSH and GSH-derivatives during mass spectrometry analysis allowed us to demonstrate that reversible intramolecular H-atom transfer reactions between GS• and C-H bonds at Cys[αC], Cys[βC], and Gly[αC] are possible
Atypical birdsong and artificial languages provide insights into how communication systems are shaped by learning, use and transmission
In this article, I argue that a comparative approach focusing on the cognitive capacities and behavioral mechanisms that underlie vocal learning in songbirds and humans can provide valuable insights into the evolutionary origins of language. The experimental approaches I discuss use abnormal song and atypical linguistic input to study the processes of individual learning, social interaction, and cultural transmission. Atypical input places increased learning and communicative pressure on learners, so exploring how they respond to this type of input provides a particularly clear picture of the biases and constraints at work during learning and use. Furthermore, simulating the cultural transmission of these unnatural communication systems in the laboratory informs us about how learning and social biases influence the structure of communication systems in the long run. Findings based on these methods suggest fundamental similarities in the basic social–cognitive mechanisms underlying vocal learning in birds and humans, and continuing research promises insights into the uniquely human mechanisms and into how human cognition and social behavior interact, and ultimately impact on the evolution of language
A tale of two stories: astrocyte regulation of synaptic depression and facilitation
Short-term presynaptic plasticity designates variations of the amplitude of
synaptic information transfer whereby the amount of neurotransmitter released
upon presynaptic stimulation changes over seconds as a function of the neuronal
firing activity. While a consensus has emerged that changes of the synapse
strength are crucial to neuronal computations, their modes of expression in
vivo remain unclear. Recent experimental studies have reported that glial
cells, particularly astrocytes in the hippocampus, are able to modulate
short-term plasticity but the underlying mechanism is poorly understood. Here,
we investigate the characteristics of short-term plasticity modulation by
astrocytes using a biophysically realistic computational model. Mean-field
analysis of the model unravels that astrocytes may mediate counterintuitive
effects. Depending on the expressed presynaptic signaling pathways, astrocytes
may globally inhibit or potentiate the synapse: the amount of released
neurotransmitter in the presence of the astrocyte is transiently smaller or
larger than in its absence. But this global effect usually coexists with the
opposite local effect on paired pulses: with release-decreasing astrocytes most
paired pulses become facilitated, while paired-pulse depression becomes
prominent under release-increasing astrocytes. Moreover, we show that the
frequency of astrocytic intracellular Ca2+ oscillations controls the effects of
the astrocyte on short-term synaptic plasticity. Our model explains several
experimental observations yet unsolved, and uncovers astrocytic
gliotransmission as a possible transient switch between short-term paired-pulse
depression and facilitation. This possibility has deep implications on the
processing of neuronal spikes and resulting information transfer at synapses.Comment: 93 pages, manuscript+supplementary text, 10 main figures, 11
supplementary figures, 1 tabl
Quantifying the Dynamics of Coupled Networks of Switches and Oscillators
Complex network dynamics have been analyzed with models of systems of coupled switches or systems of coupled oscillators. However, many complex systems are composed of components with diverse dynamics whose interactions drive the system's evolution. We, therefore, introduce a new modeling framework that describes the dynamics of networks composed of both oscillators and switches. Both oscillator synchronization and switch stability are preserved in these heterogeneous, coupled networks. Furthermore, this model recapitulates the qualitative dynamics for the yeast cell cycle consistent with the hypothesized dynamics resulting from decomposition of the regulatory network into dynamic motifs. Introducing feedback into the cell-cycle network induces qualitative dynamics analogous to limitless replicative potential that is a hallmark of cancer. As a result, the proposed model of switch and oscillator coupling provides the ability to incorporate mechanisms that underlie the synchronized stimulus response ubiquitous in biochemical systems
Dietary supplementation with hydrolyzed yeast and its effect on the performance, intestinal microbiota, and immune response of weaned piglets.
The objective of this study was to evaluate the effects of autolyzed yeast on performance, cecal microbiota, and leukogram of weaned piglets. A total of 96 piglets of commercial line weaned at 21-day-old were used. The experimental design was a randomized block design with four treatments (diets containing 0.0%, 0.3%, 0.6%, and 0.9% autolyzed yeast), eight replicates, and three animals per pen in order to evaluate daily weight gain, daily feed intake, and feed conversion in periods of 0 to 15, 0 to 26, and 0 to 36 days. Quadratic effects of autolyzed yeast inclusion were observed on the feed conversion from 0 to 15 days, on daily weight gain from 0 to 15 days, 0 to 26 days and, 0 to 36 days, indicating an autolyzed yeast optimal inclusion level between 0.4% and 0.5%. No effect from autolyzed yeast addition was observed on piglet daily feed intake, cecal microbiota, and leukogram; however, i.m. application of E. coli lipopolysaccharide reduced the values of total leukocytes and their fractions (neutrophils, eosinophils, lymphocytes, monocytes, and rods). Therefore, autolyzed yeast when provided at levels between 0.4% and 0.5% improved weaned piglets’ performance.info:eu-repo/semantics/publishedVersio
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