Y-Like Retinal Ganglion Cells Innervate the Dorsal Raphe Nucleus in the Mongolian Gerbil (Meriones unguiculatus)

Background: The dorsal raphe nucleus (DRN) of the mesencephalon is a complex multi-functional and multi-transmitter nucleus involved in a wide range of behavioral and physiological processes. The DRN receives a direct input from the retina. However little is known regarding the type of retinal ganglion cell (RGC) that innervates the DRN. We examined morphological characteristics and physiological properties of these DRN projecting ganglion cells. Methodology/Principal Findings: The Mongolian gerbils are highly visual rodents with a diurnal/crepuscular activity rhythm. It has been widely used as experimental animals of various studies including seasonal affective disorders and depression. Young adult gerbils were used in the present study. DRN-projecting RGCs were identified following retrograde tracer injection into the DRN, characterized physiologically by extracellular recording and morphologically after intracellular filling. The result shows that DRN-projecting RGCs exhibit morphological characteristics typical of alpha RGCs and physiological response properties of Y-cells. Melanopsin was not detected in these RGCs and they show no evidence of intrinsic photosensitivity. Conclusions/Significance: These findings suggest that RGCs with alpha-like morphology and Y-like physiology appear to perform a non-imaging forming function and thus may participate in the modulation of DRN activity which includes regulation of sleep and mood

Visual response patterns of Y cells before and after synaptic transmission blockade.

<p>The synaptic blocker cocktail consisted of a mixture of excitatory and inhibitory neurotransmitter blockers including L-(+)-2-Amino-4-phosphonobutyric acid (AP-4, 100 µM), 6,7-Dinitroquinoxaline-2,3-dione (DNQX, 20 µM), DL-2-amino-5-phosphonovaleric acid (AP5, 50 µM), Picrotoxin (50 µM ) Strychnine (0.3 µM), and hexamethonimm bromide (200 µM) was added to the oxygenated Ames' medium. (<b>A</b>) visual responses of an ON center (upper) and (<b>C</b>) an OFF center (lower) DRN-projecting RGCs before synaptic transmission blockade. (<b>B</b>) and (<b>D</b>) response patterns of the cells after synaptic transmission blockade. The retinal irradiance of the stimuli was 6.4×10¹³ photons/cm²/sec, λ = 475 nm, and stimulation duration was 20 seconds.</p

The distribution pattern of DRN-projecting RGCs.

<p>(<b>A</b>) the distribution pattern of DRN-projecting RGCs in a wholemount retina, (<b>B</b>) two neighboring alpha cells from the retina that have overlapped dendritic fields, (<b>C</b>) DRN-projecting alpha cells distributed in a small retinal area, (<b>D</b>) Higher-magnification view of overlapped dendritic fields of the two cells in (<b>B</b>), Arrow heads show possible synaptic contacts between the two, (<b>E</b>) double labeled RGCs innervate both DRN (red fluorescent staining) and dLGN (green fluorescent staining). (<b>F</b>) double labeled RGCs send their bifurcating axons to both DRN (red fluorescent staining) and SC (green fluorescent staining). The open arrows show RGCs projecting both nuclei and solid arrows illustrate RGCs project to dLGN or SC. The arrow head depicts a RGC that projects to DRN only. Dendritic field size and soma size variation with retinal eccentricity are provided in (<b>G</b>) and (<b>H</b>). Scale bars: A: 1 mm; B: 100 µm; C: 500 µm; D: 25 µm.</p

Physiological response properties of the DRN-projecting RGCs.

<p>(<b>A</b>) the visual response of an ON center Y-cell, (<b>B</b>) receptive field, and (<b>C</b>), dendritic morphology; the arrow reveals axon, (<b>D</b>) spatial frequency tuning of a Y-cell. Note the cell's response reached peak at 0.07 c/d. 3E presents the peristimulus-time histograms of the cell's responses to contrast reversal sinusoidal gratings (spatial frequency: 0.07 cyc/deg, temporal frequency: 2 Hz, contrast: 100%). The numbers to the left of the histograms depict spatial phases. This cell had frequency doubling at two spatial phases, 0° and 180°, respectively. 2F illustrates that, after fast Fourier transformation, the fundamental component (F1) is represented by triangular symbols (Δ) while the second harmonic (F2) is shown with open circular symbols (o).</p

Dendritic morphology of DRN-projecting RGCs.

<p>(<b>A</b>) the DRN injection site. The arrow points to the injection site. (<b>B</b>)–(<b>D</b>) morphology of intracellularly injected DRN-projecting RGCs. (<b>B</b>) a large dendritic field alpha cell, (<b>C</b>) a relatively small dendritic field alpha cell, (<b>D</b>) a three dimensional reconstructed DRN-projecting alpha cell immunohistochemically stained with (FITC) and a melanopsin cell immunocytochemically stained for melanopsin (red); note lack of melanopsin immunoreactivity in DRN-projecting RGC. (<b>E</b>) morphology of a DRN-projecting non-alpha cell. The Arrows depict the axon. Scale bars: (<b>A</b>): 500 µm; (<b>B</b>): 200 µm; (<b>C</b>): 100 µm; (<b>D</b>): 100 µm; (<b>E</b>): 60 µm.</p

Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility

To access publisher's full text version of this article click on the hyperlink at the bottom of the pageTo further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.Canadian Institutes of Health Research Medical Research Council UK G0601261 Mexico Convocatoria SSA/IMMS/ISSSTE-CONACYT 2012-2 clave 150352 IMSS R-2011-785-018 CONACYT Salud-2007-C01-71068 US National Institutes of Health DK062370 HG000376 DK085584 DK085545 DK073541 DK085501 Wellcome Trust WT098017 WT090532 WT090367 WT098381 WT081682 WT085475info:eu-repo/grantAgreement/EC/FP7/20141