ON and OFF retinal ganglion cells differentially regulate serotonergic and GABAergic activity in the dorsal raphe nucleus

The dorsal raphe nucleus (DRN), the major source of serotonergic input to the forebrain, receives excitatory input from the retina that can modulate serotonin levels and depressive-like behavior. In the Mongolian gerbil, retinal ganglion cells (RGCs) with alpha-like morphological and Y-like physiological properties innervate the DRN with ON DRN-projecting RGCs out numbering OFF DRN-projecting RGCs. The DRN neurons targeted by ON and OFF RGCs are unknown. To explore retino-raphe anatomical organization, retinal afferents labeled with Cholera toxin B were examined for association with the postsynaptic protein PSD-95. Synaptic associations between retinal afferents and DRN serotonergic and GABAergic neurons were observed. To explore retino-raphe functional organization, light-evoked c-fos expression was examined. Light significantly increased the number of DRN serotonergic and GABAergic cells expressing c-Fos. When ON RGCs were rendered silent while enhancing the firing rate of OFF RGCs, c-Fos expression was greatly increased in DRN serotonergic neurons suggesting that OFF DRN-projecting RGCs predominately activate serotonergic neurons whereas ON DRN-projecting RGCs mainly target GABAergic neurons. Direct glutamatergic retinal input to DRN 5-HT neurons contributes to the complex excitatory drive regulating these cells. Light, via the retinoraphe pathway can modify DRN 5-HT neuron activity which may play a role in modulating affective behavior

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

Physiological Effects of Superoxide Dismutase on Altered Visual Function of Retinal Ganglion Cells in db/db Mice

Background: The C57BLKS/J db/db (db/db) mouse is a widely used type 2 diabetic animal model, and this model develops early inner retinal neuronal dysfunction beginning at 24 weeks. The neural mechanisms that mediate early stage retinal dysfunction in this model are unknown. We evaluated visual response properties of retinal ganglion cells (RGCs) during the early stage of diabetic insult (8, 12, and 20 wk) in db/db mice and determined if increased oxidative stress plays a role in impaired visual functions of RGCs in 20 wk old db/db mice. Methodology/Principal Findings: In vitro extracellular single-unit recordings from RGCs in wholemount retinas were performed. The receptive field size, luminance threshold, and contrast gain of the RGCs were investigated. Although ONand OFF-RGCs showed a different time course of RF size reduction, by 20 wk, the RF of ON- and OFF-RGCs were similarly affected. The LT of ON-RGCs was significantly elevated in 12 and 20 wk db/db mice compared to the LT of OFF-RGCs. The diabetic injury also affected contrast gains of ON- and OFF-RGCs differently. The generation of reactive oxidative species (ROS) in fresh retina was estimated by dihydroethidium. Superoxide dismutase (SOD) (300 unit/ml) was applied in Ames medium to the retina, and visual responses of RGCs were recorded for five hours. ROS generation in the retinas of db/db mice increased at 8wk and continued to progress at 20 wk of ages. In vitro application of SOD improved visual functions in 20 wk db/db mice but the SOD treatment affected ON- and OFF-RGCs differently in db/m retina

Visual Response Properties of Y Cells in the Detached Feline Retina Visual Neurophysiology

PURPOSE. To evaluate early changes in the visual response properties of Y cells in the detached feline retina. METHODS. The retinas of young adult cats were detached by injection, with a glass micropipette, of a solution of 0.004% sodium hyaluronate in a balanced salt solution between the neural retina and the retinal pigment epithelium. At 1, 3, and 7 days after detachment, the eyes were removed. The eyecup was prepared as a flat mount in a recording chamber and superfused with medium. Extracellular single-unit responses from Y cells in the retinas were recorded. RESULTS. One, 3, and 7 days after retinal detachment surgery, Y cells showed clear signs of functional deterioration. At each time point, more ON center cells than OFF cells were encountered. Y cells in the detached retinas showed a statistically significant elevation in the average threshold irradiance after 1-, 3-, and 7-day detachment, respectively. The average contrast threshold recorded from cells in the normal retina was 3.6%, but it increased to 14.5%, 21.8%, and 47.5% after 1-, 3-, and 7-day detachment, respectively. Furthermore, at each time point, the capability of Y cells to process contrast information decreased significantly more because of detachment than because of luminance task performance. CONCLUSIONS. Retinal detachment induced rapid functional remodeling that resulted in degenerated Y-cell function, including an elevated luminance threshold and a deteriorated contrast threshold. Detachment had a greater impact on the latter. These physiological changes after retinal detachment could be used as objective indicators of early deterioration of visual function in future studies of retinal remodeling. (Invest Ophthalmol Vis Sci. 2010;51:1208 -1215 This is partly attributed to the intrinsic nature of photoreceptor cells, in that outer segments are able to regenerate after reattachment and that most of them achieve near-normal morphologies. Nevertheless, visual deficits are common after successful reattachment surgery. 7-9 Regardless of the initial insult, stressed photoreceptors can remodel their synaptic terminals and their relationship to second-order neurons. These changes are proposed to progress through three phases: photoreceptor stress, photoreceptor death, and complex neural remodeling. 10 Although the cells are in detachment, neural remodeling occurs early-within a few days-and, therefore, before massive photoreceptor cell death. Substantial evidence suggests that diagnosis and intervention at the early stages of retinal remodeling, especially during the stress phase, when there is significant photoreceptor terminal modifications, are critical for the successful rescue of injured cells and the restoration of visual function. Over the years, molecular and morphologic changes during this stage have been explicitly addressed in experimental retinal detachment, 3 whereas objective neurophysiological observations correlating these early structural changes have been reported only in data from electroretinography. 11 Electroretinographic (ERG) testing provides one objective measurement of the electrical activity of detached and reattached retinas. 12-16 However, current ERG technology is not sensitive enough to detect alterations at the single-cell level. RGCs play the crucial role in collecting appropriate input from second-order neurons and transmitting visual information to higher visual centers, but little is known about the functional consequence of these neurons after RD and subsequent reattachment. Y cells have been studied for more than 40 years, From th

Experimental Study on the Stability of a Novel Nanocomposite-Enhanced Viscoelastic Surfactant Solution as a Fracturing Fluid under Unconventional Reservoir Stimulation

Fe3O4@ZnO nanocomposites (NCs) were synthesized to improve the stability of the wormlike micelle (WLM) network structure of viscoelastic surfactant (VES) fracturing fluid and were characterized by Fourier transform infrared spectrometry (FT-IR), scanning electron microscopy (SEM), energy dispersive spectrometry (EDS), X-ray diffraction (XRD) and vibrating sample magnetometry (VSM). Then, an NC-enhanced viscoelastic surfactant solution as a fracturing fluid (NC-VES) was prepared, and its properties, including settlement stability, interactions between NCs and WLMs, proppant-transporting performance and gel-breaking properties, were systematically studied. More importantly, the influences of the NC concentration, shear rate, temperature and pH level on the stability of NC-VES were systematically investigated. The experimental results show that the NC-VES with a suitable content of NCs (0.1 wt.%) shows superior stability at 95 °C or at a high shear rate. Meanwhile, the NC-VES has an acceptable wide pH stability range of 6–9. In addition, the NC-VES possesses good sand-carrying performance and gel-breaking properties, while the NCs can be easily separated and recycled by applying a magnetic field. The temperature-resistant, stable and environmentally friendly fracturing fluid opens an opportunity for the future hydraulic fracturing of unconventional reservoirs

Number of caudal periaqueductal gray (cPAG)-projecting retinal ganglion cells (RGCs) required to tile up the retinal surface.

<p>The calculations are used to determine the number of cPAG-projecting RGCs that are required to cover the whole retinal surface. The size of the retinal surface area is referred from Fite’s study <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103306#pone.0103306-Fite1" target="_blank">[11]</a>; tiling up the whole retinal surface is generally considered as a criterion for a type of RGC, and our results indicate approximately 1300 cPAG-projecting RGCs are required to cover the whole retinal surface in this species.</p

Dendritic fields that sometimes overlap with one another among caudal periaqueductal gray (cPAG)-projecting retinal ganglion cells (RGCs).

<p>(A) Intracellularly injected cPAG-projecting RGCs in a whole-mounted retina. S: superior; I: inferior; N: nasal; T: temporal. (B) The white box in (A) viewed under high magnification. In this field three neighboring cPAG-projecting RGCs that have overlapped dendritic fields were labeled with three different colors (magenta, yellow and green). (C) Three dimensional reconstruction of overlapped dendritic fields. IPL: inner plexiform layer; a: sublamina <i>a</i> of inner plexiform layer; b: sublamina <i>b</i> of inner plexiform layer. Scale bars: 1 mm in A; 20 µm in B; 10 µm in C.</p

Variation in the sizes of dendritic fields and somata with retinal eccentricity.

<p>(A) Plot of dendritic field diameter as a function of eccentricity. (B) Plot of soma diameter as a function of eccentricity. 7 animals were used in each analysis.</p