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Exposure to stressors has profound effects on sleep that have been linked to serotonin (5-HT) neurons of the dorsal raphe nucleus (DR). However, the DR also comprises glutamatergic neurons expressing vesicular glutamate transporter type 3 (DRVGLUT3), leading us to examine their role. Cell-type-specific tracing revealed that DRVGLUT3 neurons project to brain areas regulating arousal and stress. We found that chemogenetic activation of DRVGLUT3 neurons mimics stress-induced sleep perturbations. Furthermore, deleting VGLUT3 in the DR attenuated stress-induced sleep perturbations, especially after social defeat stress. In the DR, VGLUT3 is found in subsets of 5-HT and non-5-HT neurons. We observed that both populations are activated by acute stress, including those projecting to the ventral tegmental area. However, deleting VGLUT3 in 5-HT neurons minimally affected sleep regulation. These findings suggest that VGLUT3 expression in the DR drives stress-induced sleep perturbations, possibly involving non-5-HT DRVGLUT3 neurons. [Display omitted] • VGLUT3 expression identifies subsets of 5-HT and non-5-HT DR neurons activated by acute stress • Selective activation of VGLUT3-expressing neurons in the DR modulates wake and REMS • Reduced VGLUT3 expression in the DR attenuates stress-induced sleep perturbations • VGLUT3 expression in 5-HT neurons exerts minimal influence on sleep Psychological stressors can induce maladaptive disruptions in sleep patterns. Henderson et al. show that neurons expressing VGLUT3 in the dorsal raphe nucleus (DR) are involved in the stress response and contribute to the circuit mechanisms mediating the effects of acute stress on sleep. [ABSTRACT FROM AUTHOR]

Abstract: We study the extraction of Δ-resonance parameters from lattice data for small quark masses, corresponding to the case of an unstable Δ. To this end, we calculate the spectrum of the correlator of two Δ-fields in a finite Euclidean box up-to-and-including in the small scale expansion using infrared regularization. On the basis of our numerical study, we argue that the extraction of the parameters of the Δ-resonance (in particular, of the mass and the pion–nucleon–delta coupling constant) from the measured volume dependence of the lowest energy levels should be feasible. [Copyright &y& Elsevier]

Abstract: Theoretical as well as experimental progress has been made in the last decade in describing the properties of baryons. In this review I will mostly report on the theoretical issues. Two non-perturbative methods are privileged frameworks for studying their properties in the low-energy domain: chiral perturbation theory, the effective field theory of the Standard Model at energies below 1 GeV and lattice QCD. I will mainly concentrate here on the first one but I will also discuss the complementarity of the two methods. Chiral extrapolations for lattice simulations of some nucleon properties will be investigated. I will then concentrate on processes involving at most two nucleons, describing for example pion–nucleon and pion–deuteron scattering, pion photo- and electro-production off the nucleon and the deuteron and doubly virtual Compton scattering. Three flavor calculations will also be reviewed. [Copyright &y& Elsevier]

Abstract: At the neuromuscular junction (NMJ) acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) can hydrolyze acetylcholine (ACh). Released ACh quanta are known to diffuse rapidly across the narrow synaptic cleft and pairs of ACh molecules cooperate to open endplate channels. During their diffusion through the cleft, or after being released from muscle nicotinic ACh receptors (nAChRs), most ACh molecules are hydrolyzed by AChE highly concentrated at the NMJ. Advances in mouse genomics offered new approaches to assess the role of specific cholinesterases involved in synaptic transmission. AChE knockout mice (AChE-KO) provide a valuable tool for examining the complete abolition of AChE activity and the role of BChE. AChE-KO mice live to adulthood, and exhibit an increased sensitivity to BChE inhibitors, suggesting that BChE activity facilitated their survival and compensated for AChE function. Our results show that BChE is present at the endplate region of wild-type and AChE-KO mature muscles. The decay time constant of focally recorded miniature endplate currents was 1.04±0.06 ms in wild-type junctions and 5.4 ms±0.3 ms in AChE-KO junctions, and remained unaffected by BChE-specific inhibitors, indicating that BChE is not limiting ACh duration on endplate nAChRs. Inhibition of BChE decreased evoked quantal ACh release in AChE-KO NMJs. This reduction in ACh release can explain the greatest sensitivity of AChE-KO mice to BChE inhibitors. BChE is known to be localized in perisynaptic Schwann cells, and our results strongly suggest that BChE''s role at the NMJ is to protect nerve terminals from an excess of ACh. [Copyright &y& Elsevier]

Abstract: Clean tests of a small admixture of right-handed quark currents directly coupled to the standard W are still lacking. We show that such non-standard couplings can be significantly constrained measuring the value of the scalar Kπ form factor at the Callan–Treiman point to a few percent. A realistic prospect of such a measurement in decay based on an accurate dispersive representation of the scalar form factor is presented. The inadequacy of the currently used linear parametrization is explained and illustrated using recent KTeV data. We briefly comment on the charged kaon mode. [Copyright &y& Elsevier]

In vitro studies have widely demonstrated that the abundance and availability of G-protein-coupled receptors (GPCRs) at the cell surface is regulated by the neuronal environment and is the result of complex intraneuronal trafficking. However, this regulation is still poorly understood in vivo. Modulation of receptor availability at the neuronal membrane is a key event in the regulation of neuronal functions (e.g. neurotransmitter release or neuronal excitability in physiological, pathological or therapeutic conditions). We discuss the effects of duration of receptor stimulation (acute versus chronic) on the intraneuronal trafficking of GPCRs in vivo, and we show that this trafficking might differ according to subcellular compartment (soma, dendrites or axon terminals). [Copyright &y& Elsevier]

Abstract: We calculate the nucleon and the delta mass to fourth order in a covariant formulation of the small scale expansion. We analyze lattice data from the MILC Collaboration and demonstrate that the available lattice data combined with our knowledge of the physical values for the nucleon and delta masses lead to consistent chiral extrapolation functions for both observables up to fairly large pion masses. This holds in particular for very recent data on the delta mass from the QCDSF Collaboration. The resulting pion–nucleon sigma term is . This first quantitative analysis of the quark-mass dependence of the structure of the in full QCD within chiral effective field theory suggests that (the real part of) the nucleon–delta mass-splitting in the chiral limit, , is slightly larger than at the physical point. Further analysis of simultaneous fits to nucleon and delta lattice data are needed for a precision determination of the properties of the first excited state of the nucleon. [Copyright &y& Elsevier]

We have studied ”in vivo” neurochemically identified striatal neurons to analyze the localisation and the trafficking of dopamine and acetylcholine G protein coupled receptors (GPCR) (D1R, D2R, m2R and m4R) under the influence of neurotransmitter environment. We have identified receptors in tissue sections through immunohistochemical detection at the light and electron microscopic level. We have identified receptors in normal animals and after acute and chronic stimulations. We have quantified receptors through image analysis at the electron microscopic level in relation to various subcellular compartments. Our results demonstrate that, in normal conditions, GPCRs are mostly associated with plasma membrane of the striatal neurons, mostly at extra-synaptic sites. In certain instances (m4R; D2R), receptors have prominent localisation inside the rough endoplasmic reticulum. Our results also show that two distinct receptors for a same neurotransmitter may have distinct subcellular localisation in a same neuronal population (m2R versus m4R) and that the same neurotransmitter receptor (m4R) can have distinct localisation in distinct neuronal populations (cytoplasm versus cell surface). After acute stimulation, cell surface receptors undergo dramatic subcellular changes that involve plasma membrane depletion, internalisation in endosomes and in multivesicular bodies. Such changes are reversible after the end of the stimulation and are blocked by antagonist action. Chronic stimulation also provokes changes in subcellular localisation with specific pattern: plasma membrane depletion, and exaggerated storage of receptors in rough endoplasmic reticulum and eventually Golgi complex (D1R; m2R and m4R). Decreasing chronic receptor stimulation reverses such changes. These results demonstrate that, ”in vivo”, in the striatum, GPCRs undergo complex intraneuronal trafficking under the influence of neurochemical environment in conditions that dramatically modulate the number of cell surface receptors available for interaction with neurotransmitters or drugs. This confirms that ”in vivo”, the trafficking and the subcellular compartmentalization of GPCRs may contribute to regulate neuronal sensitivity and neuronal interactions in physiological, experimental and pathological conditions, including in therapeutic conditions. [Copyright &y& Elsevier]

We study the chiral loop corrections to the generalized Gerasimov–Drell–Hearn sum rule of the nucleon for finite photon virtuality in the framework of a Lorentz-invariant formulation of baryon chiral perturbation theory. We perform a complete one-loop calculation and obtain significant differences to previously found results based on the heavy baryon approach for the proton and neutron spin-dependent forward Compton amplitudes. [Copyright &y& Elsevier]

Abstract: The complete knockout of the acetylcholinesterase gene (AChE) in the mouse yielded a surprising phenotype that could not have been predicted from deletion of the cholinesterase genes in Drosophila, that of a living, but functionally compromised animal. The phenotype of this animal showed a sufficient compromise in motor function that precluded precise characterization of central and peripheral nervous functional deficits. Since AChE in mammals is encoded by a single gene with alternative splicing, additional understanding of gene expression might be garnered from selected deletions of the alternatively spliced exons. To this end, transgenic strains were generated that deleted exon 5, exon 6, and the combination of exons 5 and 6. Deletion of exon 6 reduces brain AChE by 93% and muscle AChE by 72%. Deletion of exon 5 eliminates AChE from red cells and the platelet surface. These strains, as well as knockout strains that selectively eliminate the AChE anchoring protein subunits PRiMA or ColQ (which bind to sequences specified by exon 6) enabled us to examine the role of the alternatively spliced exons responsible for the tissue disposition and function of the enzyme. In addition, a knockout mouse was made with a deletion in an upstream intron that had been identified in differentiating cultures of muscle cells to control AChE expression. We found that deletion of the intronic regulatory region in the mouse essentially eliminated AChE in muscle and surprisingly from the surface of platelets. The studies generated by these knockout mouse strains have yielded valuable insights into the function and localization of AChE in mammalian systems that cannot be approached in cell culture or in vitro. [ABSTRACT FROM AUTHOR]

Abstract: By using immunohistochemical approaches at the light and electron microscopic levels, we have shown that aging modifies the subcellular distribution of the m2 muscarinic autoreceptor (m2R) differentially at somato-dendritic postsynaptic sites and at axonal presynaptic sites in cholinergic basalocortical neurons, in vivo. In cholinergic perikarya and dendrites of the nucleus basalis magnocellularis (NBM), aging is associated with a decrease of the density of m2R at the plasma membrane and in the cytoplasm, suggesting a decrease of the total number of m2R in the somato-dendritic field. In contrast, the number of substance P receptors per somato-dendritic surface was not affected. In the frontal cortex (FC), we have shown a decrease of cytoplasmic m2R density also leading to a decrease of the number of m2R per surface of varicosities but with no change of the density of m2R at the membrane. Our results suggest that the decrease of m2R in the somato-dendritic field of the NBM, but not a modification of the number of presynaptic m2 autoreceptors at the plasma membrane in the FC, could contribute to the decrease of the efficacy of cholinergic transmission observed with aging in the rat. [Copyright &y& Elsevier]