Direct Imaging of Hippocampal Epileptiform Calcium Motifs Following Kainic Acid Administration in Freely Behaving Mice

Prolonged exposure to abnormally high calcium concentrations is thought to be a core mechanism underlying hippocampal damage in epileptic patients; however, no prior study has characterized calcium activity during seizures in the live, intact hippocampus. We have directly investigated this possibility by combining whole-brain electroencephalographic (EEG) measurements with microendoscopic calcium imaging of pyramidal cells in the CA1 hippocampal region of freely behaving mice treated with the pro-convulsant kainic acid (KA). We observed that KA administration led to systematic patterns of epileptiform calcium activity: a series of large-scale, intensifying flashes of increased calcium fluorescence concurrent with a cluster of low-amplitude EEG waveforms. This was accompanied by a steady increase in cellular calcium levels (>5 fold increase relative to the baseline), followed by an intense spreading calcium wave characterized by a 218% increase in global mean intensity of calcium fluorescence (n = 8, range [114 - 349%], p<10-4; t-test). The wave had no consistent EEG phenotype and occurred before the onset of motor convulsions. Similar changes in calcium activity were also observed in animals treated with 2 different proconvulsant agents, N-methyl-D-aspartate (NMDA) and pentylenetetrazol (PTZ), suggesting the measured changes in calcium dynamics are a signature of seizure activity rather than a KA-specific pathology. Additionally, despite reducing the behavioral severity of KA-induced seizures, the anticonvulsant drug valproate (VA, 300 mg/kg) did not modify the observed abnormalities in calcium dynamics. These results confirm the presence of pathological calcium activity preceding convulsive motor seizures and support calcium as a candidate signaling molecule in a pathway connecting seizures to subsequent cellular damage. Integrating in vivo calcium imaging with traditional assessment of seizures could potentially increase translatability of pharmacological intervention, leading to novel drug screening paradigms and therapeutics designed to target and abolish abnormal patterns of both electrical and calcium excitation

Resilience of the Internet to random breakdowns

A common property of many large networks, including the Internet, is that the connectivity of the various nodes follows a scale-free power-law distribution, P(k)=ck^-a. We study the stability of such networks with respect to crashes, such as random removal of sites. Our approach, based on percolation theory, leads to a general condition for the critical fraction of nodes, p_c, that need to be removed before the network disintegrates. We show that for a<=3 the transition never takes place, unless the network is finite. In the special case of the Internet (a=2.5), we find that it is impressively robust, where p_c is approximately 0.99.Comment: latex, 3 pages, 1 figure (eps), explanations added, Phys. Rev. Lett., in pres

Higher-Order Explicit Methods for Laser-Plasma Interactions

The evolution of a short, intense laser pulse propagating in an underdense plasma is of particular interest for laser-plasma accelerator physics and, in some circumstances, is well-modeled by the cold Maxwell-fluid equations. Solving this system using conventional second-order explicit methods in a three-dimensional simulation over experimentally-relevant configurations is prohibitively expensive. This motivated a search for more efficient numerical methods to solve the fluid equations. Explicit methods tend to suffer from stability constraints which couple the maximum allowable time step to the spatial grid size. If the dynamics of the system evolves on a time scale much larger than the constrained time step, an explicit method would require many more update cycles than is physically necessary. In these circumstances implicit methods, which tend to be unconditionally stable, may be attractive. But when physical situations (e.g., Raman processes) need to resolve the fast dynamics, implicit methods are unlikely to exhibit much improvement over explicit methods. Thus, we look for higher-order explicit methods in space that would allow coarser spatial grids and larger time steps. We restrict our discussion to the one-dimensional case and present a comprehensive survey of a wide range of numerical methods to solve the fluid equations, including methods of order two through six in space and two through eight in time. A systematic approach to determine the stability condition is presented using linear stability analysis of numerical dispersion relations. Three higher-order methods are implemented to show their behavior, in terms of numerical stability and energy conservation

Higher-Order Explicit Numerical Methods for Laser- Plasma Interactions

The evolution of a short, intense laser pulse propagating in an underdense plasma is of particular interest for laser-plasma accelerator physics. This case is well-modeled by the cold, Maxwell–fluid equations but, using conventional second-order explicit methods, a three-dimensional simulation for experimentally relevant configurations is prohibitively expensive. This motivated a search for numerical methods that might be used to solve the fluid equations more efficiently. Explicit methods tend to suffer from stability constraints which couple the maximum allowable time step to the spatial grid size. If the dynamics of the system evolves on a time scale much larger than the constrained time step, an explicit method may require many more update cycles than is physically necessary. In these circumstances implicit methods, which tend to be unconditionally stable, may be attractive. However, in many physical situations (e.g., Raman processes) it is necessary to fully-resolve the fast dynamics. In this case, implicit methods are unlikely to exhibit much improvement over explicit methods. Thus, we look for methods of higherorder in space that would allow the use of coarser spatial grids and thus larger time steps

Fault-oriented Test Generation for Multicast Routing Protocol Design

We present a new algorithm for automatic test generation for multicast routing. Our algorithm processes a finite state machine (FSM) model of the protocol and uses a mix of forward and backward search techniques to generate the tests. The output tests include a set of topologies, protocol events and network failures, that lead to violation of protocol correctness and behavioral requirements. We target protocol robustness in specific, and do not attempt to verify other properties in this paper. We apply our method to a multicast routing protocol; PIM-DM, and investigate its behavior in the presence of selective packet loss on LANs and router crashes. Our study unveils several robustness violations in PIM-DM, for which we suggest fixes with the aid of the presented algorithm