Monitoring synaptic transmission in primary neuronal cultures using local extracellular stimulation

Various techniques have been applied for the functional analysis of synaptic transmission in Cultured neurons. Here, we describe a method of studying synaptic transmission in neurons cultured at high-density from different brain regions such as the cortex, striatum and spinal cord. We use postsynaptic whole-cell recordings to monitor synaptic Currents triggered by presynaptic action potentials that are induced by brief stimulations with a nearby extracellular bipolar electrode. Pharmacologically isolated excitatory or inhibitory postsynaptic currents can be reliably induced, with amplitudes, synaptic charge transfers, and short-term plasticity properties that are reproducible from culture to culture. We show that the size and kinetics of pharmacologically isolated inhibitory postsynaptic Currents triggered by single action potentials or stimulus trains depend on the Ca2+ concentration, temperature and stimulation frequency. This method can be applied to study synaptic transmission in wildtype neurons infected with lentiviruses encoding various components of presynaptic release machinery, or in neurons from genetically modified mice, for example neurons carrying floxed genes in which gene expression can be acutely ablated by expression of Cre recombinase. The preparation described in this paper should be useful for analysis of synaptic transmission in inter-neuronal synapses formed by different types of neurons. (c) 2006 Elsevier B.V. All rights reserved

Quantifying modeling uncertainties when combining multiple gravitational-wave detections from binary neutron star sources

With the increasing sensitivity of gravitational-wave detectors, we expect to observe multiple binary neutron-star systems through gravitational waves in the near future. The combined analysis of these gravitational-wave signals offers the possibility to constrain the neutron-star radius and the equation of state of dense nuclear matter with unprecedented accuracy. However, it is crucial to ensure that uncertainties inherent in the gravitational-wave models will not lead to systematic biases when information from multiple detections are combined. To quantify waveform systematics, we perform an extensive simulation campaign of binary neutron-star sources and analyse them with a set of four different waveform models. Based on our analysis with about 38 simulations, we find that statistical uncertainties in the neutron-star radius decrease to $\pm 250\rm m$ ($2\%$ at $90\%$ credible interval) but that systematic differences between currently employed waveform models can be twice as large. Hence, it will be essential to ensure that systematic biases will not become dominant in inferences of the neutron-star equation of state when capitalizing on future developments

Tailoring of motional states in double-well potentials by time-dependent processes

We show that the vibrational state tailoring method developed for molecular systems can be applied for cold atoms in optical lattices. The original method is based on a three-level model interacting with two strong laser pulses in a counterintuitive sequence [M. Rodriguez et al., Phys. Rev. A 62, 053413 (2000)]. Here we outline the conditions for achieving similar dynamics with single time-dependent potential surfaces. It is shown that guided switching between diabatic and adiabatic evolution has an essential role in this system. We also show that efficient and precise tailoring of motional states in optical lattices can be achieved, for instance, simply by superimposing two lattices and moving them with respect to each other.Comment: 9 pages, 11 figures, 25 references; accepted to PRA; v2: minor explanatory remarks added & typos correcte

Critical Nature of Non-Fermi Liquid in Spin 3/2 Multipolar Kondo Model

A multipolar Kondo model of an impurity spin S_I=3/2 interacting with conduction electrons with spin s_c=3/2 is investigated using boundary conformal field theory. A two-channel Kondo (2CK) -like non-Fermi liquid (NFL) under the particle-hole symmetry is derived explicitly using a ``superspin absorption'' in the sector of a hidden symmetry, SO(5). We discuss the difference between the usual spin-1/2 2CK NFL fixed point and the present one. In particular, we find that, unlike the usual 2CK model, the low temperature impurity specific heat is proportional to temperature.Comment: 4 pages, 2 figure

Preference of Small Molecules for Local Minimum Conformations when Binding to Proteins

It is well known that small molecules (ligands) do not necessarily adopt their lowest potential energy conformations when binding to proteins. Analyses of protein-bound ligand crystal structures have reportedly shown that many of them do not even adopt the conformations at local minima of their potential energy surfaces (local minimum conformations). The results of these analyses raise a concern regarding the validity of virtual screening methods that use ligands in local minimum conformations. Here we report a normal-mode-analysis (NMA) study of 100 crystal structures of protein-bound ligands. Our data show that the energy minimization of a ligand alone does not automatically stop at a local minimum conformation if the minimum of the potential energy surface is shallow, thus leading to the folding of the ligand. Furthermore, our data show that all 100 ligand conformations in their protein-bound ligand crystal structures are nearly identical to their local minimum conformations obtained from NMA-monitored energy minimization, suggesting that ligands prefer to adopt local minimum conformations when binding to proteins. These results both support virtual screening methods that use ligands in local minimum conformations and caution about possible adverse effect of excessive energy minimization when generating a database of ligand conformations for virtual screening

Normal-Mode-Analysis–Monitored Energy Minimization Procedure for Generating Small–Molecule Bound Conformations

The energy minimization of a small molecule alone does not automatically stop at a local minimum of the potential energy surface of the molecule if the minimum is shallow, thus leading to folding of the molecule and consequently hampering the generation of the bound conformation of a guest in the absence of its host. This questions the practicality of virtual screening methods that use conformations at local minima of their potential energy surfaces (local minimum conformations) as potential bound conformations. Here we report a normal-mode-analysis–monitored energy minimization (NEM) procedure that generates local minimum conformations as potential bound conformations. Of 22 selected guest–host complex crystal structures with guest structures possessing up to four rotatable bonds, all complexes were reproduced, with guest mass–weighted root mean square deviations of <1.0 Å, through docking with the NEM–generated guest local minimum conformations. An analysis of the potential energies of these local minimum conformations showed that 22 (100%), 18 (82%), 16 (73%), and 12 (55%) of the 22 guest bound conformations in the crystal structures had conformational strain energies of less than or equal to 3.8, 2.0, 0.6, and 0.0 kcal/mol, respectively. These results suggest that (1) the NEM procedure can generate small–molecule bound conformations, and (2) guests adopt low-strain–energy conformations for complexation, thus supporting the virtual screening methods that use local minimum conformations

Pion-pair formation and the pion dispersion relation in a hot pion gas

The possibility of pion--pair formation in a hot pion gas, based on the bosonic gap equation, is pointed out and discussed in detail. The critical temperature for condensation of pion pairs (Evans--Rashid transition) is determined as a function of the pion density. As for fermions, this phase transition is signaled by the appearance of a pole in the two--particle propagator. In bose systems there exists a second, lower critical temperature, associated with the appearance of the single--particle condensate. Between the two critical temperatures the pion dispersion relation changes from the usual quasiparticle dispersion to a Bogoliubov--like dispersion relation at low momenta. This generalizes the non-relativistic result for an attractive bose gas by Evans et al. Possible consequences for the inclusive pion spectra measured in heavy--ion collisions at ultra--relativistic energies are discussed.Comment: 16 pages revtex, 7 Postscript figure