Distinct forms of synaptic inhibition and neuromodulation regulate calretinin positive neuron excitability in the spinal cord dorsal horn

The dorsal horn (DH) of the spinal cord contains a heterogenous population of neurons that process incoming sensory signals before information ascends to the brain. We have recently characterized calretinin-expressing (CR+) neurons in the DH and shown that they can be divided into excitatory and inhibitory subpopulations. The excitatory population receives high-frequency excitatory synaptic input and expresses delayed firing action potential discharge, whereas the inhibitory population receives weak excitatory drive and exhibits tonic or initial bursting discharge. Here, we characterize inhibitory synaptic input and neuromodulation in the two CR+ populations, in order to determine how each is regulated. We show that excitatory CR+ neurons receive mixed inhibition from GABAergic and glycinergic sources, whereas inhibitory CR+ neurons receive inhibition, which is dominated by glycine. Noradrenaline and serotonin produced robust outward currents in excitatory CR+ neurons, predicting an inhibitory action on these neurons, but neither neuromodulator produced a response in CR+ inhibitory neurons. In contrast, enkephalin (along with selective mu and delta opioid receptor agonists) produced outward currents in inhibitory CR+ neurons, consistent with an inhibitory action but did not affect the excitatory CR+ population. Our findings show that the pharmacology of inhibitory inputs and neuromodulator actions on CR+ cells, along with their excitatory inputs can define these two subpopulations further, and this could be exploited to modulate discrete aspects of sensory processing selectively in the DH

Local and Global Casimir Energies: Divergences, Renormalization, and the Coupling to Gravity

From the beginning of the subject, calculations of quantum vacuum energies or Casimir energies have been plagued with two types of divergences: The total energy, which may be thought of as some sort of regularization of the zero-point energy, $\sum\frac12\hbar\omega$, seems manifestly divergent. And local energy densities, obtained from the vacuum expectation value of the energy-momentum tensor, $\langle T_{00}\rangle$, typically diverge near boundaries. The energy of interaction between distinct rigid bodies of whatever type is finite, corresponding to observable forces and torques between the bodies, which can be unambiguously calculated. The self-energy of a body is less well-defined, and suffers divergences which may or may not be removable. Some examples where a unique total self-stress may be evaluated include the perfectly conducting spherical shell first considered by Boyer, a perfectly conducting cylindrical shell, and dilute dielectric balls and cylinders. In these cases the finite part is unique, yet there are divergent contributions which may be subsumed in some sort of renormalization of physical parameters. The divergences that occur in the local energy-momentum tensor near surfaces are distinct from the divergences in the total energy, which are often associated with energy located exactly on the surfaces. However, the local energy-momentum tensor couples to gravity, so what is the significance of infinite quantities here? For the classic situation of parallel plates there are indications that the divergences in the local energy density are consistent with divergences in Einstein's equations; correspondingly, it has been shown that divergences in the total Casimir energy serve to precisely renormalize the masses of the plates, in accordance with the equivalence principle.Comment: 53 pages, 1 figure, invited review paper to Lecture Notes in Physics volume in Casimir physics edited by Diego Dalvit, Peter Milonni, David Roberts, and Felipe da Ros

Experimental Searches for the Axion and Axion-Like Particles

Four decades after its prediction, the axion remains the most compelling solution to the strong-CP problem and a well-motivated dark matter candidate, inspiring a host of elegant and ultrasensitive experiments based on axion-photon mixing. This article reviews the experimental situation on several fronts. The microwave cavity experiment is making excellent progress in the search for dark matter axions in the µeV range and may plausibly be extended up to 100 µeV. Within the past several years, however, researchers have realized that axions are pervasive throughout string theories, but with masses that fall naturally in the neV range, for which an NMR-based search is under development. Both searches for axions emitted from the Sun's burning core and purely laboratory experiments based on photon regeneration have recently made great progress, with ambitious projects proposed for the coming decade. Each of these campaigns has pushed the state of the art in technology, enabling large gains in sensitivity and mass reach. Furthermore, each modality has been exploited in order to search for more generalized axion-like particles, which we also discuss in this review. We are hopeful, even optimistic, that the next review of the subject will concern the discovery of the axion, its properties, and its exploitation as a probe of early universe cosmology and structure formation

Calculating Casimir Energies in Renormalizable Quantum Field Theory

Quantum vacuum energy has been known to have observable consequences since 1948 when Casimir calculated the force of attraction between parallel uncharged plates, a phenomenon confirmed experimentally with ever increasing precision. Casimir himself suggested that a similar attractive self-stress existed for a conducting spherical shell, but Boyer obtained a repulsive stress. Other geometries and higher dimensions have been considered over the years. Local effects, and divergences associated with surfaces and edges have been studied by several authors. Quite recently, Graham et al. have re-examined such calculations, using conventional techniques of perturbative quantum field theory to remove divergences, and have suggested that previous self-stress results may be suspect. Here we show that the examples considered in their work are misleading; in particular, it is well-known that in two dimensions a circular boundary has a divergence in the Casimir energy for massless fields, while for general dimension $D$ not equal to an even integer the corresponding Casimir energy arising from massless fields interior and exterior to a hyperspherical shell is finite. It has also long been recognized that the Casimir energy for massive fields is divergent for $D\ne1$. These conclusions are reinforced by a calculation of the relevant leading Feynman diagram in $D$ and three dimensions. There is therefore no doubt of the validity of the conventional finite Casimir calculations.Comment: 25 pages, REVTeX4, 1 ps figure. Revision includes new subsection 4B and Appendix, and other minor correction

Casimir Effect on the Worldline

We develop a method to compute the Casimir effect for arbitrary geometries. The method is based on the string-inspired worldline approach to quantum field theory and its numerical realization with Monte-Carlo techniques. Concentrating on Casimir forces between rigid bodies induced by a fluctuating scalar field, we test our method with the parallel-plate configuration. For the experimentally relevant sphere-plate configuration, we study curvature effects quantitatively and perform a comparison with the ``proximity force approximation'', which is the standard approximation technique. Sizable curvature effects are found for a distance-to-curvature-radius ratio of a/R >~ 0.02. Our method is embedded in renormalizable quantum field theory with a controlled treatment of the UV divergencies. As a technical by-product, we develop various efficient algorithms for generating closed-loop ensembles with Gaussian distribution.Comment: 27 pages, 10 figures, Sect. 2.1 more self-contained, improved data for Fig. 6, minor corrections, new Refs, version to be published in JHE

Vacuum local and global electromagnetic self-energies for a point-like and an extended field source

We consider the electric and magnetic energy densities (or equivalently field fluctuations) in the space around a point-like field source in its ground state, after having subtracted the spatially uniform zero-point energy terms, and discuss the problem of their singular behavior at the source's position. We show that the assumption of a point-like source leads, for a simple Hamiltonian model of the interaction of the source with the electromagnetic radiation field, to a divergence of the renormalized electric and magnetic energy density at the position of the source. We analyze in detail the mathematical structure of such singularity in terms of a delta function and its derivatives. We also show that an appropriate consideration of these singular terms solves an apparent inconsistency between the total field energy and the space integral of its density. Thus the finite field energy stored in these singular terms gives an important contribution to the self-energy of the source. We then consider the case of an extended source, smeared out over a finite volume and described by an appropriate form factor. We show that in this case all divergences in local quantities such as the electric and the magnetic energy density, as well as any inconsistency between global and space-integrated local self-energies, disappear.Comment: 8 pages. The final publication is available at link.springer.co

Functional and molecular analysis of proprioceptive sensory neuron excitability in mice

Neurons located in dorsal root ganglia (DRG) are crucial for transmitting peripheral sensations such as proprioception, touch, temperature, and nociception to the spinal cord before propagating these signals to higher brain structures. To date, difficulty in identifying modality-specific DRG neurons has limited our ability to study specific populations in detail. As the calcium-binding protein parvalbumin (PV) is a neurochemical marker for proprioceptive DRG cells we used a transgenic mouse line expressing green fluorescent protein (GFP) in PV positive DRGs, to study the functional and molecular properties of putative proprioceptive neurons. Immunolabeled DRGs showed a 100% overlap between GFP positive (GFP+) and PV positive cells, confirming the PVeGFP mouse accurately labeled PV neurons. Targeted patch-clamp recording from isolated GFP+ and GFP negative (GFP−) neurons showed the passive membrane properties of the two groups were similar, however, their active properties differed markedly. All GFP+ neurons fired a single spike in response to sustained current injection and their action potentials (APs) had faster rise times, lower thresholds and shorter half widths. A hyperpolarization-activated current (Ih) was observed in all GFP+ neurons but was infrequently noted in the GFP− population (100% vs. 11%). For GFP+ neurons, Ih activation rates varied markedly, suggesting differences in the underlying hyperpolarization-activated cyclic nucleotide-gated channel (HCN) subunit expression responsible for the current kinetics. Furthermore, quantitative polymerase chain reaction (qPCR) showed the HCN subunits 2, 1, and 4 mRNA (in that order) was more abundant in GFP+ neurons, while HCN 3 was more highly expressed in GFP− neurons. Likewise, immunolabeling confirmed HCN 1, 2, and 4 protein expression in GFP+ neurons. In summary, certain functional properties of GFP+ and GFP− cells differ markedly, providing evidence for modality-specific signaling between the two groups. However, the GFP+ DRG population demonstrates considerable internal heterogeneity when hyperpolarization-activated cyclic nucleotide-gated channel (HCN channel) properties and subunit expression are considered. We propose this heterogeneity reflects the existence of different peripheral receptors such as tendon organs, muscle spindles or mechanoreceptors in the putative proprioceptive neuron population

What is "system": the information-theoretic arguments

The problem of "what is 'system'?" is in the very foundations of modern quantum mechanics. Here, we point out the interest in this topic in the information-theoretic context. E.g., we point out the possibility to manipulate a pair of mutually non-interacting, non-entangled systems to employ entanglement of the newly defined '(sub)systems' consisting the one and the same composite system. Given the different divisions of a composite system into "subsystems", the Hamiltonian of the system may perform in general non-equivalent quantum computations. Redefinition of "subsystems" of a composite system may be regarded as a method for avoiding decoherence in the quantum hardware. In principle, all the notions refer to a composite system as simple as the hydrogen atom.Comment: 13 pages, no figure

Educating Health Professionals about Disability: A Review of Interventions

Health professionals need to understand the human rights and health needs of disabled people. This review of evidence on interventions demonstrates that a range of often innovative approaches have been trialled. Lectures by faculty are less effective in changing attitudes than contact with disabled people themselves. Existing examples of good practice need to be scaled up, and better and more long-term evaluations of impact are required