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Chad R Jackson, Noah H Green, Douglas McMahon; Retinal photoreception modulates brain serotonin function. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2374.
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Clinical and animal studies show that seasonal light signals, transduced and transmitted by the retina, are involved in mood regulation. For example, people who suffer from Seasonal Affective Disorder display alterations in retinal responses that correlate with winter time decreases in mood. The neurotransmitter serotonin is known to be important for mood regulation and the mid-brain Raphe nuclei are the sole site of serotonin production in the brain. We hypothesized that decreased retinal function would impact serotonergic function in the Raphe Nucleus. To test this hypothesis we assayed dorsal raphe 5-HT neuron activity and gene expression in strains of mice with degeneration of rod and cone photoreceptors (C3H, rd1/rd1), and loss of melanopsin photo transduction (Opn4-/-).
In vitro physiology: Dorsal raphe nuclei were placed on perforated multi-electrode arrays and recorded for serotonergic cell baseline firing rates in the presence of 40µM tryptophan and 3µM phenylepherine. Next, serotonin was perfused over the slice for 5 minutes at a concentration of 40µM to observe autoinhibition, which identifies 5-HT neurons. qRT-PCR: Mid-brains were removed, total RNA extracted, and reverse-transcribed (~250ng) into cDNA. qRT-PCR reactions were performed with 2μL cDNA, 12.5μL of SYBR Green Supermix, 8.5μL water and 1μL of 300nM forward and reverse primers in a Bio-Rad CFX96 Real-Time System. Each sample was assayed in duplicate. H&E staining: Mouse eyes were removed and dropped fixed overnight in Davidson's Fixation. Next, eyes were dehydrated in alcohol washes, placed in Xylene, and then in Paraplast Xtra. The blocks were cut at 6 μM sections, dried overnight, and stained with hematoxylin and eosin.
Mice with substantial reduction of rod and cone photoreceptors (C3H, rd1/rd1), or elimination of melanopsin from retinal ganglion cells (Opn4-/-) showed significant reductions in 5-HT neuron firing rates in vitro. Also, Opn4-/- mice displayed reductions in the expression of Tph2, and Sert, key genes regulating the synthesis and bioavailability of 5-HT, and Pet-1, which is required for the serotonergic neuron phenotype.
We found that mice with decreases in photoreception display lower serotonergic physiological function and genetic markers. These findings suggest that the visual system functionally impacts the serotongeric system and implicates it as a potential site to modulate seasonal mood disorders.
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