Hypersensitivity of Intrinsically Photosensitive Retinal Ganglion Cells in Migraine Induces Cortical Spreading Depression.

Migraine is a complex disorder characterized by episodes of moderate-to-severe, often unilateral headaches and generally accompanied by nausea, vomiting, and increased sensitivity to light (photophobia), sound (phonophobia), and smell (hyperosmia). Photophobia is considered the most bothersome symptom of migraine attacks. Although the underlying mechanism remains unclear, the intrinsically photosensitive retinal ganglion cells (ipRGCs) are considered to be involved in photophobia associated with migraine. In this study, we investigated the association between the sensitivity of ipRGCs and migraines and cortical spreading depression (CSD), which may trigger migraine attacks. The pupillary responses closely associated with the function of ipRGCs in patients with migraine who were irradiated with lights were evaluated. Blue (486 nm) light irradiation elicited a response from ipRGCs; however, red light (560 nm) had no such effect. Melanopsin, a photosensitive protein, phototransduces in ipRGCs following blue light stimulation. Hypersensitivity of ipRGCs was observed in patients with migraine. CSD was more easily induced with blue light than with incandescent light using a mouse CSD model. Moreover, CSD was suppressed, even in the presence of blue light, after injecting opsinamide, a melanopsin inhibitor. The hypersensitivity of ipRGCs in patients with migraine may induce CSD, resulting in migraine attacks.

A novel intrinsic electroretinogram response in isolated mouse retina.

Since the discovery of intrinsic photosensitive retinal ganglion cell (ipRGC) was reported in 2002, many features specific to this cell type have been described. However, scare information is available on the retinographic components directly reflecting ipRGC activity. In this study, we identified the electroretinogram (microERG) that reflects the photoresponses by ipRGCs in ex vivo preparations of the mouse retina, in which classical photoreceptors (cones and rods) were ablated mechanically and photochemically. MicroERG consisted of three components: a large transient ON response, a small and lazy hump 19s after the onset of the light, and a large transient OFF response. A complete microERG recording required at least 30s of light exposure. MicroERG showed the highest spectral photosensitivity at 478nm. This wavelength corresponds to the peak wavelength in the ipRGCs' photosensitive curve. The psychophysical test using a blue light-emitting diode (LED) light (470nm) revealed that the absolute threshold illuminance for microERG was greater than 12.26 log photons/s/cm2 in both ON and OFF responses, whereas microERG was not adapted for dark. The amplitude of microERG increased linearly with irradiance. The sensitivity of temporal frequency was high in microERG (at least 100Hz), as suggested by the study on melatonin suppression by flickering light in human subjects (Zelter et al., 2014). Melatonin secretion was suppressed by light via ipRGCs and the suprachiasmatic nucleus. These properties of the photoresponse indicate that microERG may reflect the functions of ipRGC as a luminance detector in the mouse retina.

Diurnal modulation of visual motion prediction.

Predicting the future position of moving objects is an essential cognitive function used for many daily activities, such as driving, walking and reaching. The experiments described in this paper show a marked diurnal modulation of motion prediction in inflating image perception. This motion prediction was shown to be more accurate in the afternoon than in the morning. In contrast, such modulation could not be found in deflating image perception. Such diurnal fluctuations may be mediated by circadian properties of retinal cone photoreceptors.

Problematic mobile phone use and big-five personality domains.

BACKGROUND: Although a mobile phone is useful and attractive as a tool for communication and interpersonal interaction, there exists the risk of its problematic or addictive use. OBJECTIVES: This study aims to investigate the correlation between the big-five personality domains and problematic mobile phone use. MATERIALS AND METHODS: The Mobile Phone Problem Usage Scale and the NEO Five-Factor Inventory (NEO-FFI) were employed in this study. Survey data were gathered from 504 university students for multiple regression analysis. RESULTS: Problematic mobile phone use is a function of gender, extraversion, neuroticism, openness-to-experience; however, it is not a function of agreeableness or conscientiousness. CONCLUSIONS: The measurement of these predictors would enable the screening of and intervening in the potentially problematic behaviors of mobile phone users.

Photoperiod at birth does not modulate the diurnal preference in asian population.

Two research groups reported that diurnal preference in Canadian and South European populations was modulated by the season of birth. The aim of the present study was to examine this association in the Japanese population. In this study, 1156 college students were administered the Morningness-Eveningness Questionnaire and asked the date and place of birth. Our results demonstrated that neither photoperiod nor season of birth modulated diurnal preference in the Japanese population. Two biological differences are reported to exist between Caucasians and Asians: polymorphisms of circadian clock genes and difference in ocular photosensitivity. These ethnic differences might characterize the circadian photosensitivity in infancy.

Ectopic synaptic ribbons in dendrites of mouse retinal ON- and OFF-bipolar cells.

The ectopic distribution of synaptic ribbons in dendrites of mouse retinal bipolar cells was examined by using genetic ablation of metabotropic glutamate receptor subtype 6 (mGluR6), electron microscopy, and immunocytochemistry. Ectopic ribbons were observed in dendrites of rod and ON-cone bipolar cells in the mGluR6-deficient mouse but not in those of wild-type mice. The number of rod spherules facing the ectopic ribbons in mGluR6-deficient rod bipolar dendrites increased gradually during early growth and reached a plateau level of about 20% at 12 weeks. These ectopic ribbons were immunopositive for RIBEYE, a ribbon-specific protein, but the associated vesicles were immunonegative for synaptophysin, a synaptic-vesicle-specific protein. The presence of ectopic ribbons was correlated with an increase in the roundness of the invaginating dendrites of the rod bipolar cells. We further confirmed ectopic ribbons in dendrites of OFF-cone bipolar cells in wild-type retinas. Of the four types of OFF-cone bipolar cells (T1-T4), only the T2-type, which had a greater number of synaptic ribbons at the axon terminal and a thicker axon cylinder than the other types, had ectopic ribbons. Light-adapted experiments revealed that, in wild-type mice under enhanced-light adaptation (considered similar to the mGluR6-deficient state), the roundness in the invaginating dendrites and axon terminals of rod bipolar cells increased, but no ectopic ribbons were detected. Based on these findings and known mechanisms for neurotransmitter release and protein trafficking, the possible mechanisms underlying the ectopic ribbons are discussed on the basis of intracellular transport for the replenishment of synaptic proteins.

Addictive personality and problematic mobile phone use.

Mobile phone use is banned or regulated in some circumstances. Despite recognized safety concerns and legal regulations, some people do not refrain from using mobile phones. Such problematic mobile phone use can be considered to be an addiction-like behavior. To find the potential predictors, we examined the correlation between problematic mobile phone use and personality traits reported in addiction literature, which indicated that problematic mobile phone use was a function of gender, self-monitoring, and approval motivation but not of loneliness. These findings suggest that the measurements of these addictive personality traits would be helpful in the screening and intervention of potential problematic users of mobile phones.

A novel connection between rods and ON cone bipolar cells revealed by ectopic metabotropic glutamate receptor 7 (mGluR7) in mGluR6-deficient mouse retinas.

Since the discovery of direct chemical synapses between rod photoreceptor and OFF cone bipolar cells in mouse retinas, whether the ON cone bipolar cell also receive direct chemical input from rod has been a pending question. In finding that metabotropic glutamate receptor 7 (mGluR7) was uniquely expressed in dendrites of ON cone bipolar cells in the mGluR6-deficient mouse retina, we used this ectopic mGluR7 immunoreactivity as a specific marker for the ON cone bipolar to search for its rod connection. Here, we show that a certain type of ON cone bipolar cell forms ribbon-associated synapses not only with cones, but also rods. This finding was verified in the wild-type mouse retina by three-dimensional reconstruction of bipolar cells from serial electron micrographs. These ON cone bipolars were further identified as corresponding to type 7 of mouse bipolar cell described by Ghosh et al. (2004) and also to the green fluorescent protein (GFP)-labeled type 7 bipolars in the alpha-gustducin-GFP transgenic mouse. Our findings suggest that, in mice, rod signals bifurcate into a third ON and OFF pathway in addition to the two known routes to cone bipolar cells: (1) via rod chemical synapse --> rod bipolar --> AII amacrine --> ON and OFF cone bipolar cells; (2) via rod-cone gap junction --> cone chemical synapse --> ON and OFF cone bipolar cells; and (3) via rod chemical synapse --> ON and OFF cone bipolar cells. This third novel pathway is thought to transmit fast and moderately light-sensitive rod signals, functioning to smooth out the intensity changes at the scotopic-mesopic interface.

Changes in visual response properties of cat retinal ganglion cells within two weeks after axotomy.

After optic nerve transection beta cells of cat retinal ganglion cells (RGCs) suffer from rapid cell death from 3 to 7 days, whereas alpha cells gradual cell death until 14 days. Here we report electrophysiological properties of Y- (morphological alpha) and X- (morphological beta) cells at 5 and 14 days after axotomy in comparison with those of intact Y- and X-cells. Most of the axotomized RGCs revealed characteristic visual response properties that enable us to classify them into Y- or X-cells. Physiological sampling ratio of X-cells sharply decreased from day 5 to 14 after axotomy, corresponding to the previous morphological results. As compared with intact RGCs, axotomized RGCs of both Y- and X-type revealed the following abnormalities: smaller receptive field centers, weaker visual responses and lower spontaneous activities. Intracellular injections of Lucifer yellow into axotomized and intact RGCs at eccentricities 0-6 mm from the area centralis revealed no sign of shrinkage in dendritic field size of either alpha or beta cells on day 5 and day 14 after axotomy, revealing that observed smaller receptive field centers of axotomized RGCs on day 5 were not due to the change of dendritic field sizes. These results suggest that the major events occurring shortly after axotomy are significant loss of synaptic inputs from afferent neurons in the retina and/or changes of membrane properties of axotomized RGCs. These events can also explain lower spontaneous activities and weaker visual responses of axotomized RGCs.

Phototransduction by retinal ganglion cells that set the circadian clock.

Light synchronizes mammalian circadian rhythms with environmental time by modulating retinal input to the circadian pacemaker-the suprachiasmatic nucleus (SCN) of the hypothalamus. Such photic entrainment requires neither rods nor cones, the only known retinal photoreceptors. Here, we show that retinal ganglion cells innervating the SCN are intrinsically photosensitive. Unlike other ganglion cells, they depolarized in response to light even when all synaptic input from rods and cones was blocked. The sensitivity, spectral tuning, and slow kinetics of this light response matched those of the photic entrainment mechanism, suggesting that these ganglion cells may be the primary photoreceptors for this system.