Light stimulation into dorsal raphe nucleus contributes to antidepressant effect for a stressed rat model

BackgroundLight therapy is frequently demonstrated by clinical trials to be effective to seasonal or non-seasonal major depression. However, the pathway underlying the light effect on mood remains unclear. Since a retino-raphe pathway was previously indicated to modulate 5-HT production, we hypothesize that the retinal projection into dorsal raphe nucleus (DRN) may play an important role in the light therapy for depression.MethodsA rat model of 14-day corticosterone administration (40 mg/kg/day subcutaneous injection) was mainly used to test the effect of light therapy on non-seasonal depressant-like behavior, and the involved neural circuitry and neurochemistry as well.ResultsBehavior results revealed that the bright light therapy especially with the blue light of 470 nm and 400 lux, effectively reversed the depression-like responses in those stressed rats. After elimination of retino-raphe projection using immunotoxin (Saporin) the effect of light therapy was significantly attenuated. Whereas activation of retino-raphe projection using HM3q chemogenetics was shown an effect similar to fluoxetine treatment. Furthermore, 5-HT3A positive GABA cells in the DRN were activated with high c-Fos expression that involved in an inhibition of 5-HT synthesis and a subsequent depressive behavior. While light therapy through retino-raphe projection deactivated the hyperaction of those GABA cells in the DRN; that eventually contributed to the antidepressant effect from light therapy.ConclusionsOur results indicate that the retino-raphe circuitry engaged antidepressant effect in DRN that contributed to the light therapy to the non-seasonal depression. 5-HT3A positive GABA cells in DRN was indicated to mediate this function of retino-raphe projection.