Simultaneous release of glutamate and acetylcholine from single magnocellular "cholinergic" basal forebrain neurons

Basal forebrain (BF) neurons provide the principal cholinergic drive to the hippocampus and cortex. Their degeneration is associated with the cognitive defects of Alzheimer's disease. Immunohistochemical studies suggest that some of these neurons contain glutamate, so might also release it. To test this, we made microisland cultures of single BF neurons from 12- to 14-d-old rats. Over 1-8 weeks in culture, neuronal processes made autaptic connections onto the neuron. In 34 of 36 cells tested, a somatically generated action potential was followed by a short-latency EPSC that was blocked by 1 mM kynurenic acid, showing that they released glutamate. To test whether the same neuron also released acetylcholine, we placed a voltage-clamped rat myoball expressing nicotinic receptors in contact with a neurite. In six of six neurons tested, the glutamatergic EPSC was accompanied by a nicotinic (hexamethonium-sensitive) myoball current. Stimulation of the M-2-muscarinic presynaptic receptors ( characterized using tripitramine and pirenzepine) produced a parallel inhibition of autaptic glutamatergic and myoball nicotinic responses; metabotropic glutamate receptor stimulation produced similar but less consistent and weaker effects. Atropine enhanced the glutamatergic EPSCs during repetitive stimulation by 25 +/- 6%; the anti-cholinesterase neostigmine reduced the train EPSCs by 37 +/- 6%. Hence, synaptically released acetylcholine exerted a negative-feedback inhibition of coreleased glutamate. We conclude that most cholinergic basal forebrain neurons are capable of releasing glutamate as a cotransmitter and that the release of both transmitters is subject to simultaneous feedback inhibition by synaptically released acetylcholine. This has implications for BF neuron function and for the use of cholinesterase inhibitors in Alzheimer's disease

On vortex/wave interactions. Part 2. Originating from axisymmetric flow with swirl

Following the study in Part 1 of cross-flow and other non-symmetric effects on vortex/wave interactions in boundary layers, the present Part 2 applies the ideas of Part 1 and related works to an incident axisymmetric flow supplemented by a small swirl or azimuthal velocity. This is with a view to possibly increasing understanding of vortex breakdown. The wave components involved are predominantly inviscid Rayleigh-like ones. The presence of the swirl leads to extra features and complications associated mainly with extra logarithmic contributions but for the dominant interactions essentially the same equations as in Part 1 are found. These dominant nonlinear interactions must be based on azimuthal wavenumbers of +/-1 in the case of the Squire jet with swirl. In contrast to Part 1, which consisted mainly of an analysis of the quasi-bounded solutions, a representative set of numerical solutions of the full integro-differential amplitude equations is presented, for realistic axial and swirl velocity profiles. The work points also to the influence of further increases in the incident swirl

Homology stability for outer automorphism groups of free groups

We prove that the quotient map from Aut(F_n) to Out(F_n) induces an isomorphism on homology in dimension i for n at least 2i+4. This corrects an earlier proof by the first author and significantly improves the stability range. In the course of the proof, we also prove homology stability for a sequence of groups which are natural analogs of mapping class groups of surfaces with punctures. In particular, this leads to a slight improvement on the known stability range for Aut(F_n), showing that its i-th homology is independent of n for n at least 2i+2.Comment: Published by Algebraic and Geometric Topology at http://www.maths.warwick.ac.uk/agt/AGTVol4/agt-4-54.abs.htm

Molecular simulations of entangled defect structures around nanoparticles in nematic liquid crystals

We investigate the defect structures forming around two nanoparticles in a Gay-Berne nematic liquid crystal using molecular simulations. For small separations, disclinations entangle both particles forming the figure of eight, the figure of omega and the figure of theta. These defect structures are similar in shape and occur with a comparable frequency to micron-sized particles studied in experiments. The simulations reveal fast transitions from one defect structure to another suggesting that particles of nanometre size cannot be bound together effectively. We identify the 'three-ring' structure observed in previous molecular simulations as a superposition of the different entangled and non-entangled states over time and conclude that it is not itself a stable defect structure.Comment: keywords: molecular-simulation, defects, nematic, disclination, algorithmic classification ; 8 pages, 7 figures, 1 tabl

A Review of the Open Educational Resources (OER) Movement: Achievements, Challenges, and New Opportunities

Examines the state of the foundation's efforts to improve educational opportunities worldwide through universal access to and use of high-quality academic content

Visual Responses in Mice Lacking Critical Components of All Known Retinal Phototransduction Cascades

The mammalian visual system relies upon light detection by outer-retinal rod/cone photoreceptors and melanopsin-expressing retinal ganglion cells. Gnat1(-/-); Cnga3(-/-); Opn4(-/-) mice lack critical elements of each of these photoreceptive mechanisms via targeted disruption of genes encoding rod alpha transducin (Gnat1); the cone-specific alpha 3 cyclic nucleotide gated channel subunit (Cnga3); and melanopsin (Opn4). Although assumed blind, we show here that these mice retain sufficiently widespread retinal photoreception to drive a reproducible flash electroretinogram (ERG). The threshold sensitivity of this ERG is similar to that of cone-based responses, however it is lost under light adapted conditions. Its spectral efficiency is consistent with that of rod opsin, but not cone opsins or melanopsin, indicating that it originates with light absorption by the rod pigment. The TKO light response survives intravitreal injection of U73122 (a phospholipase C antagonist), but is inhibited by a missense mutation of cone alpha transducin (Gnat2(cpfl3)), suggesting Gnat2-dependence. Visual responses in TKO mice extend beyond the retina to encompass the lateral margins of the lateral geniculate nucleus and components of the visual cortex. Our data thus suggest that a Gnat1-independent phototransduction mechanism downstream of rod opsin can support relatively widespread responses in the mammalian visual system. This anomalous rod opsin-based vision should be considered in experiments relying upon Gnat1 knockout to silence rod phototransduction

Study to define and verify the personal oral hygiene requirements for extended manned space flight Annual report, 1 Jul. 1968 - 30 Jun. 1969

Astronaut oral hygiene requirements for extended manned space fligh

Coupled Fluids-Radiation Analysis of a High-Mass Mars Vehicle

The NEQAIR line-by-line radiation code has been incorporated into the DPLR Navier-Stokes flow solver such that the NEQAIR subroutines are now callable functions of DPLR. The coupled DPLR-NEQAIR code was applied to compute the convective and radiative heating rates over high-mass Mars entry vehicles. Two vehicle geometries were considered - a 15 m diameter 70-degree sphere cone configuration and a slender, mid-L/D vehicle with a diameter of 5 m called an Ellipsled. The entry masses ranged from 100 to 165 metric tons. Solutions were generated for entry velocities ranging from 6.5 to 9.1 km/s. The coupled fluids-radiation solutions were performed at the peak heating location along trajectories generated by the Traj trajectory analysis code. The impact of fluids-radiation coupling is a function of the level of radiative heating and the freestream density and velocity. For the high-mass Mars vehicles examined in this study, coupling effects were greatest for entry velocities above 8.5 km/s where the surface radiative heating was reduced by up 17%. Generally speaking, the Ellipsled geometry experiences a lower peak radiative heating rate but a higher peak turbulent convective heating rate than the MSL-based vehicle