Direct Retino-Raphe Projection Alters Serotonergic Tone and Affective Behavior

Abstract

Light is a powerful modulator of higher-order cognitive processes such as mood but it remains unclear which neural circuits mediate the impact of light on affective behavior. We found that light deprivation produces a depressive-like behavioral state that is reversed by activation of direct retinal signals to the serotonergic dorsal raphe nucleus (DRN) in a manner equivalent to treatment with the selective serotonin reuptake inhibitor fluoxetine. Surprisingly, the DRN-projecting retinal ganglion cells (RGCs) are indistinguishable from the classic alpha/Y-like RGC type that contributes to image-forming visual pathways. Silencing RGC firing or specific immunotoxin ablation of DRN-projecting RGCs increased depressive-like behavior and reduced serotonin levels in the DRN. Serotonin has a key role in the pathophysiology of depression, and these results demonstrate that retino-raphe signals modulate DRN serotonergic tone and affective behavior.

Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin

“…The immobility time was applied as the indicator for behavioral despair. The sucrose preference test (SPT) was performed as previously reported (25). Data were presented as the percentage of sucrose consumption.…”

Dendritic Morphology of Caudal Periaqueductal Gray Projecting Retinal Ganglion Cells in Mongolian Gerbil (Meriones unguiculatus)

“…In our previous work, morphological and physiological properties of direct dorsal raphe nuclei (DRN)-projecting retinal ganglion cells (RGCs) in Mongolian gerbil were described [4]. We also found that the changes in the activities of DRN-projecting Y/alpha cells could directly modulate the level of serotonin in serotonergic neurons in DRN and influence the depressive behavior [5].…”

Intrinsically Photosensitive Retinal Ganglion Cell Activity Is Associated with Decreased Sleep Quality in Patients with Glaucoma

“…Intrinsically photosensitive retinal ganglion cells (ipRGCs) constitute a type of ganglion cell that express the photopigment melanopsin 9e12 and mediate "nonvisual" responses to light (e.g., regulating the photic synchronization of circadian rhythms 12e15 and the pupillary light reflex, 16 as well as modulating behavioral mood regulation and memory). 17,18 The true impact of glaucoma on sleep quality, sleep disturbance, or circadian rhythm is controversial. Jakobs et al 19 reported that ipRGC degeneration was proportional to that of the entire ganglion cell population.…”