Combined Unilateral Blockade of Cholinergic, Peptidergic, And Serotonergic Receptors in The Ventral Respiratory Column Does Not Affect Breathing in Awake Or Sleeping Goats

Previous work in intact awake and sleeping goats has found that unilateral blockade of excitatory inputs in the ventral respiratory column (VRC) elicits changes in the concentrations of multiple neurochemicals, including serotonin (5-HT), substance P, glycine, and GABA, while increasing or having no effect on breathing. These findings are consistent with the concept of interdependence between neuromodulators, whereby attenuation of one modulator elicits compensatory changes in other modulators to maintain breathing. Because there is a large degree of redundancy and multiplicity of excitatory inputs to the VRC, we herein tested the hypothesis that combined unilateral blockade of muscarinic acetylcholine (mACh), neurokinin-1 (NK1, the receptor for substance P), and 5-HT2A receptors would elicit changes in multiple neurochemicals, but would not change breathing. We unilaterally reverse-dialyzed a cocktail of antagonists targeting these receptors into the VRC of intact adult goats. Breathing was continuously monitored while effluent fluid from dialysis was collected for quantification of neurochemicals. We found that neither double blockade of mACh and NK1 receptors, nor triple blockade of mACh, NK1, and 5-HT2A receptors significantly affected breathing (P ≥ 0.05) in goats that were awake or in non-rapid eye movement (NREM) sleep. However, both double and triple blockade increased the effluent concentration of substance P (P \u3c 0.001) and decreased GABA concentrations. These findings support our hypothesis and, together with past data, suggest that both in wakefulness and NREM sleep, multiple neuromodulator systems collaborate to stabilize breathing when a deficit in one or multiple excitatory neuromodulators exists

Hypnotics' association with mortality or cancer: a matched cohort study

Objectives: An estimated 6%e10 % of US adults took a hypnotic drug for poor sleep in 2010. This study extends previous reports associating hypnotics with excess mortality. Setting: A large integrated health system in the USA. Design: Longitudinal electronic medical records were extracted for a one-to-two matched cohort survival analysis. Subjects: Subjects (mean age 54 years) were 10 529 patients who received hypnotic prescriptions and 23 676 matched controls with no hypnotic prescriptions, followed for an average of 2.5 year

Effects on Breathing of Agonists to μ-opioid or GABA\u3csub\u3eA\u3c/sub\u3e Receptors Dialyzed into the Ventral Respiratory Column of Awake and Sleeping Goats

Pulmonary ventilation (V̇I) in awake and sleeping goats does not change when antagonists to several excitatory G protein-coupled receptors are dialyzed unilaterally into the ventral respiratory column (VRC). Concomitant changes in excitatory neuromodulators in the effluent mock cerebral spinal fluid (mCSF) suggest neuromodulatory compensation. Herein, we studied neuromodulatory compensation during dialysis of agonists to inhibitory G protein-coupled or ionotropic receptors into the VRC. Microtubules were implanted into the VRC of goats for dialysis of mCSF mixed with agonists to either μ-opioid (DAMGO) or GABAA (muscimol) receptors. We found: (1) V̇I decreased during unilateral but increased during bilateral dialysis of DAMGO, (2) dialyses of DAMGO destabilized breathing, (3) unilateral dialysis of muscimol increased V̇I, and (4) dialysis of DAMGO decreased GABA in the effluent mCSF. We conclude: (1) neuromodulatory compensation can occur during altered inhibitory neuromodulator receptor activity, and (2) the mechanism of compensation differs between G protein-coupled excitatory and inhibitory receptors and between G protein-coupled and inotropic inhibitory receptors

State-Dependent and -Independent Effects of Dialyzing Excitatory Neuromodulator Receptor Antagonists into the Ventral Respiratory Column

Unilateral dialysis of the broad-spectrum muscarinic receptor antagonist atropine (50 mM) into the ventral respiratory column [(VRC) including the pre-Bötzinger complex region] of awake goats increased pulmonary ventilation (V̇i) and breathing frequency (f), conceivably due to local compensatory increases in serotonin (5-HT) and substance P (SP) measured in effluent mock cerebral spinal fluid (mCSF). In contrast, unilateral dialysis of a triple cocktail of antagonists to muscarinic (atropine; 5 mM), neurokinin-1, and 5-HT receptors does not alter V̇i or f, but increases local SP. Herein, we tested hypotheses that 1) local compensatory 5-HT and SP responses to 50 mM atropine dialyzed into the VRC of goats will not differ between anesthetized and awake states; and 2) bilateral dialysis of the triple cocktail of antagonists into the VRC of awake goats will not alter V̇i or f, but will increase local excitatory neuromodulators. Through microtubules implanted into the VRC of goats, probes were inserted to dialyze mCSF alone (time control), 50 mM atropine, or the triple cocktail of antagonists. We found 1) equivalent increases in local 5-HT and SP with 50 mM atropine dialysis during wakefulness compared with isoflurane anesthesia, but V̇i and f only increased while awake; and 2) dialyses of the triple cocktail of antagonists increased V̇i, f, 5-HT, and SP

SKA Deep Polarization and Cosmic Magnetism

Deep surveys with the SKA1-MID array offer for the first time the opportunity to systematically explore the polarization properties of the microJy source population. Our knowledge of the polarized sky approaching these levels is still very limited. In total intensity the population will be dominated by star-forming and normal galaxies to intermediate redshifts ($z \sim1-2$), and low-luminosity AGN to high redshift. The polarized emission from these objects is a powerful probe of their intrinsic magnetic fields and of their magnetic environments. For redshift of order 1 and above the broad bandwidth of the mid-bands span the Faraday thick and thin regimes allowing study of the intrinsic polarization properties of these objects as well as depolarization from embedded and foreground plasmas. The deep field polarization images will provide Rotation Measures data with very high solid angle density allowing a sensitive statistical analysis of the angular variation of RM on critical arc-minute scales from a magnetic component of Large Scale Structure of the Universe.Comment: 9 pages, 3 figures; to appear as part of 'Cosmic Magnetism' in Proceedings 'Advancing Astrophysics with the SKA (AASKA14)', PoS(AASKA14)11

Hubble Space Telescope WFPC-2 Imaging of Cassiopeia A

The young SNR Cassiopeia A was imaged with WFPC-2 through four filters selected to capture the complete velocity range of the remnant's main shell in several important emission lines. Primary lines detected were [O III] 4959,5007, [N II] 6583, [S II] 6716,6731 + [O II] 7319,7330 + [O I] 6300,6364, and [S III] 9069,9532. About 3/4th of the remnant's main shell was imaged in all four filters. Considerable detail is observed in the reverse-shocked ejecta with typical knot scale lengths of 0.2"-0.4" (1 - 2 x 10^16 cm). Both bright and faint emission features appear highly clumped. Large differences in [S III] and [O III] line intensities indicating chemical abundance differences are also seen, particularly in knots located along the bright northern limb and near the base of the northeast jet. A line of curved overlapping filament in the remnant's northwestern rim appears to mark the location of the remnant's reverse shock front in this region. Finger-like ejecta structures elsewhere suggest cases where the reverse shock front is encountering the remnant's clumped ejecta. Narrow-band [N II] images of the remnant's circumstellar knots ("QSFs") reveal them to be 0.1"-0.6" thick knots and filaments, often with diffuse edges facing away from the center of expansion. Three color composite images of the whole remnant and certain sections along with individual filter enlargements of selected regions of the bright optical shell are presented and discussed.Comment: 26 pages, 12 figures Accepted to the Astronomical Journa