title: Light evokes melanopsin-dependent vocalization and neural activation associated with aversive experience in neonatal mice.
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.
authors.affiliation: Department of Ophthalmology, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Anton
authors.initials: A
authors.lastname: Delwig
authors.forename: Anne M
authors.initials: AM
authors.lastname: Logan
authors.forename: David R
authors.initials: DR
authors.lastname: Copenhagen
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Ahn
mesh_terms: D000679:Amygdala / Q000378:metabolism; D000818:Animals; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008027:Light; D051379:Mice; D010775:Photic Stimulation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D017299:Rod Opsins / Q000378:metabolism*; D013788:Thalamus / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000378:metabolism; D014785:Vision, Ocular / Q000502:physiology; D014828:Vocalization, Animal / Q000502:physiology*; D000099210:Melanopsin
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D016760:Proto-Oncogene Proteins c-fos; D017299:Rod Opsins; D000099210:Melanopsin