Origin and Functional Impact of Dark Noise in Retinal Cones

AbstractSpontaneous fluctuations in the electrical signals of the retina's photoreceptors impose a fundamental limit on visual sensitivity. While noise in the rods has been studied extensively, relatively little is known about the noise of cones. We show that the origin of the dark noise in salamander cones varies with cone type. Most of the noise in long wavelength–sensitive (L) cones arose from spontaneous activation of the photopigment, which is a million-fold less stable than the rod photopigment rhodopsin. Most of the noise in short wavelength–sensitive (S) cones arose in a later stage of the transduction cascade, as the photopigment was relatively stable. Spontaneous pigment activation effectively light adapted L cones in darkness, causing them to have a smaller and briefer dim flash response than S cones

Network Variability Limits Stimulus-Evoked Spike Timing Precision in Retinal Ganglion Cells

SummaryVisual, auditory, somatosensory, and olfactory stimuli generate temporally precise patterns of action potentials (spikes). It is unclear, however, how the precision of spike generation relates to the pattern and variability of synaptic input elicited by physiological stimuli. We determined how synaptic conductances evoked by light stimuli that activate the rod bipolar pathway control spike generation in three identified types of mouse retinal ganglion cells (RGCs). The relative amplitude, timing, and impact of excitatory and inhibitory input differed dramatically between On and Off RGCs. Spikes evoked by repeated somatic injection of identical light-evoked synaptic conductances were more temporally precise than those evoked by light. However, the precision of spikes evoked by conductances that varied from trial to trial was similar to that of light-evoked spikes. Thus, the rod bipolar pathway modulates different RGCs via unique combinations of synaptic input, and RGC temporal variability reflects variability in the input this circuit provides

Speed of synchronization in complex networks of neural oscillators Analytic results based on Random Matrix Theory

We analyze the dynamics of networks of spiking neural oscillators. First, we present an exact linear stability theory of the synchronous state for networks of arbitrary connectivity. For general neuron rise functions, stability is determined by multiple operators, for which standard analysis is not suitable. We describe a general non-standard solution to the multi-operator problem. Subsequently, we derive a class of rise functions for which all stability operators become degenerate and standard eigenvalue analysis becomes a suitable tool. Interestingly, this class is found to consist of networks of leaky integrate and fire neurons. For random networks of inhibitory integrate-and-fire neurons, we then develop an analytical approach, based on the theory of random matrices, to precisely determine the eigenvalue distribution. This yields the asymptotic relaxation time for perturbations to the synchronous state which provides the characteristic time scale on which neurons can coordinate their activity in such networks. For networks with finite in-degree, i.e. finite number of presynaptic inputs per neuron, we find a speed limit to coordinating spiking activity: Even with arbitrarily strong interaction strengths neurons cannot synchronize faster than at a certain maximal speed determined by the typical in-degree.Comment: 17 pages, 12 figures, submitted to Chao

A Spitzer Survey of Protoplanetary Disk Dust in the Young Serpens Cloud: How do Dust Characteristics Evolve with Time?

We present Spitzer IRS mid-infrared (5-35 micron) spectra of a complete flux-limited sample (> 3 mJy at 8 micron) of young stellar object (YSO) candidates selected on the basis of their infrared colors in the Serpens Molecular Cloud. Spectra of 147 sources are presented and classified. Background stars (with slope consistent with a reddened stellar spectrum and silicate features in absorption), galaxies (with redshifted PAH features) and a planetary nebula (with high ionization lines) amount to 22% of contamination in this sample, leaving 115 true YSOs. Sources with rising spectra and ice absorption features, classified as embedded Stage I protostars, amount to 18% of the sample. The remaining 82% (94) of the disk sources are analyzed in terms of spectral energy distribution shapes, PAHs and silicate features. The presence, strength and shape of these silicate features are used to infer disk properties for these systems. About 8% of the disks have 30/13 micron flux ratios consistent with cold disks with inner holes or gaps, and 3% of the disks show PAH emission. Comparison with models indicates that dust grains in the surface of these disks have sizes of at least a few \mu\m. The 20 micron silicate feature is sometimes seen in absence of the 10 micron feature, which may be indicative of very small holes in these disks. No significant difference is found in the distribution of silicate feature shapes and strengths between sources in clusters and in the field. Moreover, the results in Serpens are compared with other well-studied samples: the c2d IRS sample distributed over 5 clouds and a large sample of disks in the Taurus star-forming region. The remarkably similar distributions of silicate feature characteristics in samples with different environment and median ages - if significant - imply that the dust population in the disk surface results from an equilibrium between dust growth and destructive collision processes that are maintained over a few million years for any YSO population irrespective of environment.Comment: accepted by Ap

Coordinated control of sensitivity by two splice variants of Gαo in retinal ON bipolar cells

The high sensitivity of scotopic vision depends on the efficient retinal processing of single photon responses generated by individual rod photoreceptors. At the first synapse in the mammalian retina, rod outputs are pooled by a rod “ON” bipolar cell, which uses a G-protein signaling cascade to enhance the fidelity of the single photon response under conditions where few rods absorb light. Here we show in mouse rod bipolar cells that both splice variants of the Go α subunit, Gαo1 and Gαo2, mediate light responses under the control of mGluR6 receptors, and their coordinated action is critical for maximizing sensitivity. We found that the light response of rod bipolar cells was primarily mediated by Gαo1, but the loss of Gαo2 caused a reduction in the light sensitivity. This reduced sensitivity was not attributable to the reduction in the total number of Go α subunits, or the altered balance of expression levels between the two splice variants. These results indicate that Gαo1 and Gαo2 both mediate a depolarizing light response in rod bipolar cells without occluding each other’s actions, suggesting they might act independently on a common effector. Thus, Gαo2 plays a role in improving the sensitivity of rod bipolar cells through its action with Gαo1. The coordinated action of two splice variants of a single Gα may represent a novel mechanism for the fine control of G-protein activity

Spectroscopic time series performance of the Mid-Infrared Instrument on the JWST

We present here the first ever mid-infrared spectroscopic time series observation of the transiting exoplanet \object{L 168-9 b} with the Mid-Infrared Instrument (MIRI) on the James Webb Space Telescope. The data were obtained as part of the MIRI commissioning activities, to characterize the performance of the Low Resolution Spectroscopy (LRS) mode for these challenging observations. To assess the MIRI LRS performance, we performed two independent analyses of the data. We find that with a single transit observation we reached a spectro-photometric precision of $\sim$50 ppm in the 7-8 \micron range at R=50, consistent with $\sim$25 ppm systematic noise. The derived band averaged transit depth is 524 $\pm$ 15 ppm and 547 $\pm$ 13 ppm for the two applied analysis methods, respectively, recovering the known transit depth to within 1 $\sigma$. The measured noise in the planet's transmission spectrum is approximately 15-20 \% higher than random noise simulations over wavelengths $6.8 \lesssim \lambda \lesssim 11$ $\mu$m. \added{We observed an larger excess noise at the shortest wavelengths of up to a factor of two, for which possible causes are discussed.} This performance was achieved with limited in-flight calibration data, demonstrating the future potential of MIRI for the characterization of exoplanet atmospheres.Comment: Accepted for publishing in PASP, 21 pages, 10 figure

Pharmacological and rAAV Gene Therapy Rescue of Visual Functions in a Blind Mouse Model of Leber Congenital Amaurosis

BACKGROUND: Leber congenital amaurosis (LCA), a heterogeneous early-onset retinal dystrophy, accounts for ~15% of inherited congenital blindness. One cause of LCA is loss of the enzyme lecithin:retinol acyl transferase (LRAT), which is required for regeneration of the visual photopigment in the retina. METHODS AND FINDINGS: An animal model of LCA, the Lrat (−/−) mouse, recapitulates clinical features of the human disease. Here, we report that two interventions—intraocular gene therapy and oral pharmacologic treatment with novel retinoid compounds—each restore retinal function to Lrat (−/−) mice. Gene therapy using intraocular injection of recombinant adeno-associated virus carrying the Lrat gene successfully restored electroretinographic responses to ~50% of wild-type levels (p < 0.05 versus wild-type and knockout controls), and pupillary light responses (PLRs) of Lrat (−/−) mice increased ~2.5 log units (p < 0.05). Pharmacological intervention with orally administered pro-drugs 9-cis-retinyl acetate and 9-cis-retinyl succinate (which chemically bypass the LRAT-catalyzed step in chromophore regeneration) also caused long-lasting restoration of retinal function in LRAT-deficient mice and increased ERG response from ~5% of wild-type levels in Lrat (−/−) mice to ~50% of wild-type levels in treated Lrat (−/−) mice (p < 0.05 versus wild-type and knockout controls). The interventions produced markedly increased levels of visual pigment from undetectable levels to 600 pmoles per eye in retinoid treated mice, and ~1,000-fold improvements in PLR and electroretinogram sensitivity. The techniques were complementary when combined. CONCLUSION: Intraocular gene therapy and pharmacologic bypass provide highly effective and complementary means for restoring retinal function in this animal model of human hereditary blindness. These complementary methods offer hope of developing treatment to restore vision in humans with certain forms of hereditary congenital blindness

Empfehlungen der Ständigen Impfkommission (STIKO) und der Deutschen Gesellschaft für Tropenmedizin, Reisemedizin und Globale Gesundheit e.V. (DTG) zu Reiseimpfungen

Die STIKO empfiehlt Reiseimpfungen zum individuellen Schutz Reisender mit einem Expositionsrisiko gegenüber bestimmten impfpräventablen Erkrankungen und um den Import von Infektionserregern in das bereiste Land oder bei Rückreise nach Deutschland zu verhindern. Die im Epidemiologischen Bulletin 14/2023 veröffentlichten Empfehlungen zu Reiseimpfungen wurden von der STIKO-AG Reiseimpfungen in Zusammenarbeit mit externen Expertinnen und Experten erarbeitet. Neuerungen sind dabei u. a. die aktualisierte Epidemiologie bei Cholera, Hepatitis A, Hepatitis B, Meningokokken und Typhus sowie eine umfassende Literatur-Aktualisierung.Peer Reviewe