Activity-dependent adenosine release may be linked to activation of Na+-K+ ATPase : an in vitro rat study

In the brain, extracellular adenosine increases as a result of neuronal activity. The mechanisms by which this occurs are only incompletely understood. Here we investigate the hypothesis that the Na+ influxes associated with neuronal signalling activate the Na+-K+ ATPase which, by consuming ATP, generates intracellular adenosine that is then released via transporters. By measuring adenosine release directly with microelectrode biosensors, we have demonstrated that AMPA-receptor evoked adenosine release in basal forebrain and cortex depends on extracellular Na+. We have simultaneously imaged intracellular Na+ and measured adenosine release. The accumulation of intracellular Na+ during AMPA receptor activation preceded adenosine release by some 90 s. By removing extracellular Ca2+, and thus preventing indiscriminate neuronal activation, we used ouabain to test the role of the Na+-K+ ATPase in the release of adenosine. Under conditions which caused a Na+ influx, brief applications of ouabain increased the accumulation of intracellular Na+ but conversely rapidly reduced extracellular adenosine levels. In addition, ouabain greatly reduced the amount of adenosine released during application of AMPA. Our data therefore suggest that activity of the Na+-K+ ATPase is directly linked to the efflux of adenosine and could provide a universal mechanism that couples adenosine release to neuronal activity. The Na+-K+ ATPase-dependent adenosine efflux is likely to provide adenosine-mediated activity-dependent negative feedback that will be important in many diverse functional contexts including the regulation of sleep

Wakefulness affects synaptic and network activity by increasing extracellular astrocyte-derived adenosine

Loss of sleep causes an increase in sleep drive and deficits in hippocampal-dependent memory. Both of these responses are thought to require activation of adenosine A1 receptors (adorA1Rs) and release of transmitter molecules including ATP, which is rapidly converted to adenosine in the extracellular space, from astrocytes in a process termed gliotransmission. Although it is increasingly clear that astrocyte-derived adenosine plays an important role in driving the homeostatic sleep response and the effects of sleep loss on memory (Halassa et al., 2009; Florian et al., 2011), previous studies have not determined whether the concentration of this signaling molecule increases in response to wakefulness. Here, we show that the level of adorA1R activation increases in response to wakefulness in mice (Mus musculus). We found that this increase affected synaptic transmission in the hippocampus and modulated network activity in the cortex. Direct biosensor-based measurement of adenosine showed that the net extracellular concentration of this transmitter increased in response to normal wakefulness and sleep deprivation. Genetic inhibition of gliotransmission prevented this increase and attenuated the wakefulness-dependent changes in synaptic and network regulation by adorA1R. Consequently, we conclude that wakefulness increases the level of extracellular adenosine in the hippocampus and that this increase requires the release of transmitters from astroctyes

Differences in transmission properties and susceptibility to long-term depression reveal functional specialization of ascending axon and parallel fiber synapses to Purkinje cells

An understanding of the patterns of mossy fiber transmission to Purkinje cells, via granule cell axons, is fundamental to models of cerebellar cortical signaling and processing. Early theories assumed that mossy fiber input is widely disseminated across the cerebellar cortex along beams of parallel fibers, which spread for several millimeters across the cerebellar cortex. Direct evidence for this has, however, proved controversial, leading to the development of an alternative hypothesis that mossy fiber inputs to the cerebral cortex are in fact vertically organized such that the ascending segment of the granule axon carries a greater synaptic weight than the parallel fiber segment. Here, we report that ascending axon synapses are selectively resistant to cerebellar long-term depression and that they release transmitter with higher mean release probabilities and mean quantal amplitudes than parallel fiber synapses. This novel specialization of synapses formed by different segments of the same axon not only explains the reported patterns of granule cell→ Purkinje cell transmission across the cerebellar cortex but also reveals an additional level of functionality and complexity of cerebellar processing. Consequently, ascending axon synapses represent a new element of cortical signal processing that should be distinguished from parallel fiber synapses in future experimental and theoretical studies of cerebellar function

Propagation of Correlations in Quantum Lattice Systems

We provide a simple proof of the Lieb-Robinson bound and use it to prove the existence of the dynamics for interactions with polynomial decay. We then use our results to demonstrate that there is an upper bound on the rate at which correlations between observables with separated support can accumulate as a consequence of the dynamics.Comment: 10 page

Absence of reflection as a function of the coupling constant

We consider solutions of the one-dimensional equation $-u'' +(Q+ \lambda V) u = 0$ where $Q: \mathbb{R} \to \mathbb{R}$ is locally integrable, $V : \mathbb{R} \to \mathbb{R}$ is integrable with supp$(V) \subset [0,1]$, and $\lambda \in \mathbb{R}$ is a coupling constant. Given a family of solutions $\{u_{\lambda} \}_{\lambda \in \mathbb{R}}$ which satisfy $u_{\lambda}(x) = u_0(x)$ for all $x<0$, we prove that the zeros of $b(\lambda) := W[u_0, u_{\lambda}]$, the Wronskian of $u_0$ and $u_{\lambda}$, form a discrete set unless $V \equiv 0$. Setting $Q(x) := -E$, one sees that a particular consequence of this result may be stated as: if the fixed energy scattering experiment $-u'' + \lambda V u = Eu$ gives rise to a reflection coefficient which vanishes on a set of couplings with an accumulation point, then $V \equiv 0$.Comment: To appear in Journal of Mathematical Physic

An hp-adaptive discontinuous Galerkin method for phase field fracture

The phase field method is becoming the de facto choice for the numerical analysis of complex problems that involve multiple initiating, propagating, interacting, branching and merging fractures. However, within the context of finite element modelling, the method requires a fine mesh in regions where fractures will propagate, in order to capture sharp variations in the phase field representing the fractured/damaged regions. This means that the method can become computationally expensive when the fracture propagation paths are not known a priori. This paper presents a 2D -adaptive discontinuous Galerkin finite element method for phase field fracture that includes a posteriori error estimators for both the elasticity and phase field equations, which drive mesh adaptivity for static and propagating fractures. This combination means that it is possible to be reliably and efficiently solve phase field fracture problems with arbitrary initial meshes, irrespective of the initial geometry or loading conditions. This ability is demonstrated on several example problems, which are solved using a light-BFGS (Broyden–Fletcher–Goldfarb–Shanno) quasi-Newton algorithm. The examples highlight the importance of driving mesh adaptivity using both the elasticity and phase field errors for physically meaningful, yet computationally tractable, results. They also reveal the importance of including -refinement, which is typically not included in existing phase field literature. The above features provide a powerful and general tool for modelling fracture propagation with controlled errors and degree-of-freedom optimised meshes

Changing the Custody of Children Whose Parents Have Been Divorced: A General View of the Process

The purpose of this project was to obtain a preliminary description, through study of the legal files, of that group of persons who appear before the Court of Domestic Relations for a reconsideration of the custody decision made initially, at the time of divorce. A sample of 92 cases heard in Multnomah County in 1965 was obtained. A survey of the literature revealed that much of what has been written on the subject of divorce and custody is primarily from a statistical or legalistic standpoint and very little bears directly on the granting or obtaining of custody or the problems encountered by the custodial or non-custodial parents and the children. A reading schedule was developed for the purpose of recording the information in the legal files maintained by the court. The characteristics of the sample group were tallied in an effort to obtain a statistical profile of that group requiring additional court appearances to settle the matter of custody. A number of hypotheses were developed and tested by means of Chi Square. Though this study was limited by the fact that no control group was used and no personal interviews were obtained, it clearly indicates the need for additional research in the area of divorce and custody and suggestions are made for future projects

Tusk or Bone? An Example of Ivory Substitute in the Wildlife Trade

Bone carvings (and other ivory substitutes) are common in the modern-day lucrative international ivory trade.  Souvenirs for unknowing travelers and market shoppers can be made of non-biological material (plastic "ivory" beads) or skillfully crafted natural objects made to resemble something other than their true origin.  Many of these items are received at the U. S. National Fish and Wildlife Forensics Laboratory (NFWFL) for species identification as part of law enforcement investigations.  Morphologists at the Lab often receive uniquely carved ivory items that have been imported with little or no documentation.  In recent years, analysts examined several purported ivory tusks suspected to be walrus, a protected marine mammal.  After examination, the Lab determined their origin as carved leg bones of cattle using principles and methods of zooarchaeology and ancient DNA analysis.  The naturally long and straight ungulate metapodials had been cut, carved, filled, stained, and polished to closely resemble unmodified ivory tusks.  Morphological species identification of these bones proved to be a challenge since diagnostic characters of the bones had been altered and country of origin was unknown. Genetic analysis showed that the bones originated from cattle.  While bone is commonly used as a substitute for ivory, this style of artifact was not previously documented in the wildlife trade prior to our analysis.  Archaeological ethnobiologists commonly encounter bone tools and other forms of material culture from prehistoric and historic contexts; in this case bone tools come from a modern context, thus the application of methods common in zooarchaeology are situated in wildlife forensics.  In addition, results reported here pertain to cross-cultural ivory trade and conservation science.</p

A Multi-Dimensional Lieb-Schultz-Mattis Theorem

For a large class of finite-range quantum spin models with half-integer spins, we prove that uniqueness of the ground state implies the existence of a low-lying excited state. For systems of linear size L, of arbitrary finite dimension, we obtain an upper bound on the excitation energy (i.e., the gap above the ground state) of the form (C\log L)/L. This result can be regarded as a multi-dimensional Lieb-Schultz-Mattis theorem and provides a rigorous proof of a recent result by Hastings.Comment: final versio