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: 3.23). 09/2012; 7(9):e43787. DOI: 10.1371/journal.pone.0043787
Source: PubMed


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.

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    • "Ultrasonic vocalizations (USVs) from mouse pups were recorded with an ultrasound detector (UltraSound Advice, UK; model: mini-3) and a sound recorder (Sony PCM-M10). Timing of USVs was detected offline by thresholding the root mean square levels (5 msec bins; Matlab) as described previously [2]. Movement of pups was quantified by frame differencing [19] as the number of pixels that changed their intensity value more than the threshold. "
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    ABSTRACT: Melanopsin-expressing retinal ganglion cells (mRGCs) in the eye play an important role in many light-activated non-image-forming functions including neonatal photoaversion and the adult pupillary light reflex (PLR). MRGCs rely on glutamate and possibly PACAP (pituitary adenylate cyclase-activating polypeptide) to relay visual signals to the brain. However, the role of these neurotransmitters for individual non-image-forming responses remains poorly understood. To clarify the role of glutamatergic signaling from mRGCs in neonatal aversion to light and in adult PLR, we conditionally deleted vesicular glutamate transporter (VGLUT2) selectively from mRGCs in mice. We found that deletion of VGLUT2 in mRGCs abolished negative phototaxis and light-induced distress vocalizations in neonatal mice, underscoring a necessary role for glutamatergic signaling. In adult mice, loss of VGLUT2 in mRGCs resulted in a slow and an incomplete PLR. We conclude that glutamatergic neurotransmission from mRGCs is required for neonatal photoaversion but is complemented by another non-glutamatergic signaling mechanism for the pupillary light reflex in adult mice. We speculate that this complementary signaling might be due to PACAP neurotransmission from mRGCs.
    Full-text · Article · Dec 2013 · PLoS ONE
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    • "At a developmental stage in which only ipRGCs are photoreceptive, pups turn away from blue light, a response lacking in melanopsin-deficient mice.94 This response was accompanied by ultrasonic vocalizations, which are used by rodents to communicate threats or danger, and activation of the posterior thalamus (implicated in migraine-related pain95) and the central amygdala (associated with nociception96). A direct role for ipRGCs in light aversion was also shown for adult mice. Innate light aversion, which is revealed by prior environmental and light exposure, is decreased in mice lacking ipRGCs but not rod and cone photoreceptors.97,98 "
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    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.
    Preview · Article · Sep 2013 · Journal of Experimental Neuroscience
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    ABSTRACT: It is now a decade since the first published reports that a small proportion of mammalian retinal ganglion cells are directly photoresponsive. These cells have been termed intrinsically photosensitive retinal ganglion cells (ipRGCs) and comprise a small proportion of the total population of retinal ganglion cells. The demonstration that these ganglion cells respond to light even when isolated from the rest of the retina established them as potentially autonomous photoreceptors, overturning the dogma that all visual information originates with rods and cones. It also provided a focus for what has developed into a new branch of visual science. Here we place the discovery of ipRGCs into context and review the development of this field over the last decade, with particular emphasis on prospects for practical application.
    No preview · Article · Feb 2013 · Current biology: CB
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