Intracellular Astrocyte Calcium Waves In Situ Increase the Frequency of Spontaneous AMPA Receptor Currents in CA1 Pyramidal Neurons

Spontaneous neurotransmitter release and activation of group I metabotropic glutamate receptors (mGluRs) each play a role in the plasticity of neuronal synapses. Astrocytes may contribute to short- and long-term synaptic changes by signaling to neurons via these processes. Spontaneous whole-cell AMPA receptor (AMPAR) currents were recorded in CA1 pyramidal cell

Performance of Sensitivity based NMPC Updates in Automotive Applications

In this work we consider a half car model which is subject to unknown but measurable disturbances. To control this system, we impose a combination of model predictive control without stabilizing terminal constraints or cost to generate a nominal solution and sensitivity updates to handle the disturbances. For this approach, stability of the resulting closed loop can be guaranteed using a relaxed Lyapunov argument on the nominal system and Lipschitz conditions on the open loop change of the optimal value function and the stage costs. For the considered example, the proposed approach is realtime applicable and corresponding results show significant performance improvements of the updated solution with respect to comfort and handling properties.Comment: 6 pages, 2 figure

Loss of IP3 Receptor-Dependent Ca2+ Increases in Hippocampal Astrocytes Does Not Affect Baseline CA1 Pyramidal Neuron Synaptic Activity

Astrocytes in the hippocampus release calcium (Ca2+) from intracellular stores intrinsically and in response to activation of Gq-linked G-protein coupled receptors (GPCRs) through the binding of inositol 1,4,5-trisphosphate (IP3) to its receptor (IP3R). Astrocyte Ca2+ has been deemed necessary and sufficient to trigger the release of gliotransmitters, such as ATP and glutamate, from astrocytes to modulate neuronal activity. Several lines of evidence suggest that IP3R Type 2 (IP3R2) is the primary IP3R expressed by astrocytes. In order to determine if IP3R2 is the primary functional IP3R responsible for astrocytic Ca2+ increases, we conducted experiments using an IP3R2 knockout mouse model (IP3R2 KO). We show for the first time that lack of IP3R2 blocks both spontaneous and Gq-linked GPCR mediated increases in astrocyte Ca2+. Furthermore, neuronal Gq-linked GPCR Ca2+ increases remain intact, suggesting that IP3R2 does not play a major functional role in neuronal calcium store release or may not be expressed in neurons. Additionally, we show that lack of IP3R2 in the hippocampus does not affect baseline excitatory neuronal synaptic activity as measured by spontaneous EPSC (sEPSC) recordings from CA1 pyramidal neurons. Whole cell recordings of the tonic NMDA receptor (NMDA-R) mediated current indicates that ambient glutamate levels are also unaffected in the IP3R2 KO. These data show that IP3R2 is the key functional IP3R driving Gq-linked GPCR mediated Ca2+ increases in hippocampal astrocytes and that removal of astrocyte Ca2+ increases does not significantly affect excitatory neuronal synaptic activity or ambient glutamate levels

Applications of sensitivity analysis for probit stochastic network equilibrium

Network equilibrium models are widely used by traffic practitioners to aid them in making decisions concerning the operation and management of traffic networks. The common practice is to test a prescribed range of hypothetical changes or policy measures through adjustments to the input data, namely the trip demands, the arc performance (travel time) functions, and policy variables such as tolls or signal timings. Relatively little use is, however, made of the full implicit relationship between model inputs and outputs inherent in these models. By exploiting the representation of such models as an equivalent optimisation problem, classical results on the sensitivity analysis of non-linear programs may be applied, to produce linear relationships between input data perturbations and model outputs. We specifically focus on recent results relating to the probit Stochastic User Equilibrium (PSUE) model, which has the advantage of greater behavioural realism and flexibility relative to the conventional Wardrop user equilibrium and logit SUE models. The paper goes on to explore four applications of these sensitivity expressions in gaining insight into the operation of road traffic networks. These applications are namely: identification of sensitive, ‘critical’ parameters; computation of approximate, re-equilibrated solutions following a change (post-optimisation); robustness analysis of model forecasts to input data errors, in the form of confidence interval estimation; and the solution of problems of the bi-level, optimal network design variety. Finally, numerical experiments applying these methods are reported

Climatic Impact of the A.D. 1783 Asama (Japan) Eruption was Minimal: Evidence from the GISP2 Ice Core

Assessing the climatic impact of the A.D. 1783 eruption of Mt. Asama, Japan, is complicated by the concurrent eruption of Laki, Iceland. Estimates of the stratospheric loading of H2SO4 for the A.D. 1108 eruption of Asama derived from the SO42− time series in the GISP2 Greenland ice core indicate a loading of about 10.4 Tg H2SO4 with a resulting stratospheric optical depth of 0.087. Assuming sulfur emissions from the 1783 eruption were only one‐third of the 1108 event yields a H2SO4 loading value of 3.5 Tg and a stratospheric optical depth of only 0.029. These results suggest minimal climatic effects in the Northern Hemisphere from the 1783 Asama eruption, thus any volcanically‐induced cooling in the mid‐1780s is probably due to the Laki eruption

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

Cortical Layer 1 and Layer 2/3 Astrocytes Exhibit Distinct Calcium Dynamics In Vivo

Cumulative evidence supports bidirectional interactions between astrocytes and neurons, suggesting glial involvement of neuronal information processing in the brain. Cytosolic calcium (Ca2+) concentration is important for astrocytes as Ca2+ surges co-occur with gliotransmission and neurotransmitter reception. Cerebral cortex is organized in layers which are characterized by distinct cytoarchitecture. We asked if astrocyte-dominant layer 1 (L1) of the somatosensory cortex was different from layer 2/3 (L2/3) in spontaneous astrocytic Ca2+ activity and if it was influenced by background neural activity. Using a two-photon laser scanning microscope, we compared spontaneous Ca2+ activity of astrocytic somata and processes in L1 and L2/3 of anesthetized mature rat somatosensory cortex. We also assessed the contribution of background neural activity to the spontaneous astrocytic Ca2+ dynamics by investigating two distinct EEG states (“synchronized” vs. “de-synchronized” states). We found that astrocytes in L1 had nearly twice higher Ca2+ activity than L2/3. Furthermore, Ca2+ fluctuations of processes within an astrocyte were independent in L1 while those in L2/3 were synchronous. Pharmacological blockades of metabotropic receptors for glutamate, ATP, and acetylcholine, as well as suppression of action potentials did not have a significant effect on the spontaneous somatic Ca2+ activity. These results suggest that spontaneous astrocytic Ca2+ surges occurred in large part intrinsically, rather than neural activity-driven. Our findings propose a new functional segregation of layer 1 and 2/3 that is defined by autonomous astrocytic activity

What Is the Role of Astrocyte Calcium in Neurophysiology?

Astrocytes comprise approximately half of the volume of the adult mammalian brain and are the primary neuronal structural and trophic supportive elements. Astrocytes are organized into distinct nonoverlapping domains and extend elaborate and dense fine processes that interact intimately with synapses and cerebrovasculature. The recognition in the mid 1990s that astrocytes undergo elevations in intracellular calcium concentration following activation of G protein-coupled receptors by synaptically released neurotransmitters demonstrated not only that astrocytes display a form of excitability but also that astrocytes may be active participants in brain information processing. The roles that astrocytic calcium elevations play in neurophysiology and especially in modulation of neuronal activity have been intensely researched in recent years. This review will summarize the current understanding of the function of astrocytic calcium signaling in neurophysiological processes and discuss areas where the role of astrocytes remains controversial and will therefore benefit from further study

Effect of acute administration of dietary Pistacia lentiscus L. essential oil on the ischemia-reperfusion-induced changes in rat frontal cortex and plasma

In this study Pistacia lentiscus L. essential oil (E.O.), a mixture of terpenes and sesquiterpenes, was tested for its protective effects in cerebral ischemia/reperfusion-induced injury in Wistar rat frontal cortex and plasma. Cerebral ischemia was produced by a 20 min bilateral common carotid artery occlusion followed by 30 min reperfusion. Pistacia lentiscus L. essential oil (E.O.) (200 mg/0, 45 ml of sunflower oil as vehicle) was administered via gavage 6 hours prior to ischemia. Rats were randomly assigned to four groups, ischemic/reperfused (I/R) and sham-operated rats treated with the vehicle or with E.O.. Different brain areas were analysed for fatty acid changes and expression of the enzyme cyclooxygenase-2 (COX-2). Ischemia/reperfusion triggered in frontal cortex a decrease of docosahexaenoic acid (DHA), the membrane highly polyunsaturated fatty acid (HPUFA) most susceptible to oxidation. Pre-treatment with E.O. prevented this change and led further to decreased levels of COX-2, as assessed by Western Blot. In plasma of ischemic/reperfused rats, E.O. administration increased both the DHA-to-eicosapentaenoic acid (EPA) ratio and levels of the endocannabinoid congeners palmytoylethanolamide (PEA) and oleoylethanolamide (OEA). The results obtained suggest that ischemia/reperfusion triggers a cerebral insult sufficient to cause a a region specific lipid peroxidation as evidenced by the detectable, significant decrease in the tissue level of DHA, the most abundant essential fatty acid of neuronal membrane phospholipids. Acute dietary pre-treatment with E.O. triggers modifications both in the frontal cortex, where COX-2 expression decreases and the decrease of DHA is apparently prevented, and in plasma, where PEA and OEA levels increase. We suggest that the activity of PEA and OEA, as endogenous ligands of the peroxisome proliferator-activated receptor (PPAR)-alpha, by inducing the peroxisomal beta oxidation, may explain the observed increase in the DHA/EPA ratio. The latter, in fact, might account for an increased metabolism of n-3 aimed at restoring DHA within damaged brain tissue. The possibility that changes in fatty acid metabolism and plasmatic availability of PEA and OEA are correlated events represents an issue worth future investigations