Dissecting a role for melanopsin in behavioural light aversion reveals a response independent of conventional photoreception.
Melanopsin photoreception plays a vital role in irradiance detection for non-image forming responses to light. However, little is known about the involvement of melanopsin in emotional processing of luminance. When confronted with a gradient in light, organisms exhibit spatial movements relative to this stimulus. In rodents, behavioural light aversion (BLA) is a well-documented but poorly understood phenomenon during which animals attribute salience to light and remove themselves from it. Here, using genetically modified mice and an open field behavioural paradigm, we investigate the role of melanopsin in BLA. While wildtype (WT), melanopsin knockout (Opn4(-/-)) and rd/rd cl (melanopsin only (MO)) mice all exhibit BLA, our novel methodology reveals that isolated melanopsin photoreception produces a slow, potentiating response to light. In order to control for the involvement of pupillary constriction in BLA we eliminated this variable with topical atropine application. This manipulation enhanced BLA in WT and MO mice, but most remarkably, revealed light aversion in triple knockout (TKO) mice, lacking three elements deemed essential for conventional photoreception (Opn4(-/-) Gnat1(-/-) Cnga3(-/-)). Using a number of complementary strategies, we determined this response to be generated at the level of the retina. Our findings have significant implications for the understanding of how melanopsin signalling may modulate aversive responses to light in mice and humans. In addition, we also reveal a clear potential for light perception in TKO mice.
Department of Ocular Biology and Therapeutics, University College London-Institute of Ophthalmology, London, United Kingdom.
Ma'ayan
M
Semo
Carlos
C
Gias
Ahmad
A
Ahmado
Eriko
E
Sugano
Annette E
AE
Allen
Jean M
JM
Lawrence
Hiroshi
H
Tomita
Peter J
PJ
Coffey
Anthony A
AA
Vugler
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects / Q000528:radiation effects*; D000075402:Channelrhodopsins; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics / Q000502:physiology; D004596:Electroretinography; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D007700:Kinetics; D008027:Light; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000528:radiation effects*; D010276:Parasympatholytics / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012044:Regression Analysis; D012160:Retina / Q000378:metabolism; D017299:Rod Opsins / Q000235:genetics / Q000502:physiology*; D015293:Transducin / Q000235:genetics / Q000502:physiology; D014793:Visual Cortex / Q000378:metabolism / Q000528:radiation effects; D000099210:Melanopsin
D001285:Atropine; D000075402:Channelrhodopsins; D054815:Cyclic Nucleotide-Gated Cation Channels; D044385:GTP-Binding Protein alpha Subunits; D010276:Parasympatholytics; D016760:Proto-Oncogene Proteins c-fos; D017299:Rod Opsins; D015293:Transducin; D000099210:Melanopsin; C518237:Cnga3 protein, mouse; C488949:Gnat1 protein, mouse