Light Evokes Melanopsin-Dependent Vocalization and Neural Activation Associated with Aversive Experience in Neonatal Mice

Department of Ophthalmology, University of California San Francisco, San Francisco, California, United States of America.
PLoS ONE (Impact Factor: 3.53). 09/2012; 7(9):e43787. DOI: 10.1371/journal.pone.0043787
Source: PubMed

ABSTRACT Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) are the only functional photoreceptive cells in the eye of newborn mice. Through postnatal day 9, in the absence of functional rods and cones, these ipRGCs mediate a robust avoidance behavior to a light source, termed negative phototaxis. To determine whether this behavior is associated with an aversive experience in neonatal mice, we characterized light-induced vocalizations and patterns of neuronal activation in regions of the brain involved in the processing of aversive and painful stimuli. Light evoked distinct melanopsin-dependent ultrasonic vocalizations identical to those emitted under stressful conditions, such as isolation from the litter. In contrast, light did not evoke the broad-spectrum calls elicited by acute mechanical pain. Using markers of neuronal activation, we found that light induced the immediate-early gene product Fos in the posterior thalamus, a brain region associated with the enhancement of responses to mechanical stimulation of the dura by light, and thought to be the basis for migrainous photophobia. Additionally, light induced the phosphorylation of extracellular-related kinase (pERK) in neurons of the central amygdala, an intracellular signal associated with the processing of the aversive aspects of pain. However, light did not activate Fos expression in the spinal trigeminal nucleus caudalis, the primary receptive field for painful stimulation to the head. We conclude that these light-evoked vocalizations and the distinct pattern of brain activation in neonatal mice are consistent with a melanopsin-dependent neural pathway involved in processing light as an aversive but not acutely painful stimulus.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Intrinsically photosensitive retinal ganglion cells (ipRGCs) are involved in circadian and other non-image forming visual responses. An open question is whether the activity of these neurons may also be under the regulation mediated by the neurohormone melatonin. In the present work, by double-staining immunohistochemical technique, we studied the expression of MT1 and MT2, two known subtypes of mammalian melatonin receptors, in rat ipRGCs. A single subset of retinal ganglion cells labeled by the specific antibody against melanopsin exhibited the morphology typical of M1-type ipRGCs. Immunoreactivity for both MT1 and MT2 receptors was clearly seen in the cytoplasm of all labeled ipRGCs, indicating that these two receptors were co-expressed in each of these neurons. Furthermore, labeling for both the receptors were found in neonatal M1 cells as early as the day of birth. It is therefore highly plausible that retinal melatonin may directly modulate the activity of ipRGCs, thus regulating non-image forming visual functions.
    PLoS ONE 02/2015; 10(2):e0117967. DOI:10.1371/journal.pone.0117967 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Mammalian vision consists of the classic image-forming pathway involving rod and cone photoreceptors interacting through a neural network within the retina before sending signals to the brain, and a non image-forming pathway that uses a photosensitive cell employing an alternative and evolutionary ancient phototransduction system and a direct connection to various centers in the brain. Intrinsically photosensitive retinal ganglion cells (ipRGCs) contain the photopigment melanopsin, which is independently capable of photon detection while also receiving synaptic input from rod and cone photoreceptors via bipolar cells. These cells are the retinal sentry for subconscious visual processing that controls circadian photoentrainment and the pupillary light reflex. Classified as irradiance detectors, recent investigations have led to expanding roles for this specific cell type and its own neural pathways, some of which are blurring the boundaries between image-forming and non image-forming visual processes.
    Journal of Experimental Neuroscience 09/2013; 7:43-50. DOI:10.4137/JEN.S11267
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose. Mutations in the RGS9 gene cause the visual disorder bradyopsia that includes difficulty adapting to changes in light and photophobia. The purpose of this study was to determine whether lack of Rgs9 also causes photophobia-like behavior in Rgs9 knockout mice (Rgs9-/-) and to identify useful diagnostic measures of Rgs9 dysfunction. Methods. We measured two behavioral responses to light and the pupillary light reflex to determine the form and basis of photophobia in Rgs9-/- mice. Results. Rgs9-/- mice spent less time in the light than wild-type mice in both dim and bright light. The mice also showed increased sensitivity to light in negative masking behavior, with a half maximal response at 0.08 lux (0.01μ in Rgs9-/- mice compared to 5.0 lux (0.85μ in wild-type mice. These behaviors were not due to increased anxiety or increased pupil size causing more light to enter the eye. Rather, constriction of the pupil showed that Rgs9-/- mice had an abnormally sustained response to light across multiple irradiance measurement pathways. Conclusions. Rgs9-/- mice recapitulate a photophobia phenotype of bradyopsia and the pupil light reflex identifies a simple means to screen for irradiance measurement abnormalities in bradyopsia and potentially other genetic disorders involving photophobia.
    Investigative Ophthalmology &amp Visual Science 09/2014; 55(10). DOI:10.1167/iovs.14-14784 · 3.66 Impact Factor

Full-text (3 Sources)

Available from
May 31, 2014