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Diego C Fernandez, Michelle Fogerson, David M Berson, Samer Hattar; Light affects mood through a novel retina-brain circuit. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4132.
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© ARVO (1962-2015); The Authors (2016-present)
Light exerts profound effects on behavior, including circadian timing and mood. Alterations in regular lighting conditions lead to mood deficits; we recently showed that this direct effect of light on mood is mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs). The goal of this study was to characterize the retina-brain circuits mediating the direct effects of light over affecting behaviors.
We used several viral and conventional axon-tracing techniques and immunofluorescence to trace pathways linking ipRGCs, through the thalamus, to the cortex. We used genetically modified mouse lines, behavioral tests, and assays of circadian genes to assess the role of these pathways in the mood effects of light.
We identified a novel retino-brain circuit that places ipRGCs just one synapse away from mood-regulating networks in the medial prefrontal cortex (mPFC) through a thalamic region, the perihabenular nucleus (PHb). Aberrant light conditions disrupt the molecular circadian clock within the PHb. Using a genetically modified mouse line that lacks ipRGC innervation to the PHb and manipulating the function of this region, we demonstrate that the PHb is necessary and sufficient for driving the adverse effects of light on mood.
These findings demonstrate that the mood-related disturbances induced by irregular light cycles are attributable to a distinct output pathway of ipRGCs that influences mood centers.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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