Brain circuits that mediate the effects of light on mood

Light has a critical impact on mood disorders in ways we are only beginning to recognize, with the potential for the development of effective, relatively non-invasive therapies. However, until now, surprisingly little has been reported on the mechanisms underlying the effects of light on mood. We characterize a newly discovered pathway that links specialized retinal photoreceptors, the dorsal thalamus, and the prefrontal cortex. This pathway apparently mediates the diverse effects of diffuse light intensity on mood. We dissect the synaptic input properties, behavioral output, and mechanistic basis of this new pathway, with special emphasis on its contribution to the pathophysiology of depression. To this end, we combine complementary behavioral, electrophysiological, functional imaging, and genetic manipulation approaches. This study, we hope, will pave the way toward a new understanding of the effect of light on mood, which can have implications both for research and in the clinic.

A newly-discovered pathway that bypasses the suprachiasmatic nucleus and regulates mood

Intrinsically photosensitive retinal ganglion cells (ipRGCs) innervate a newly-identified thalamic nucleus, the perihabenular nucleus (PHb), which in turn innervates the ventromedial prefrontal cortex (vmPFC) that has a key role in mood regulation (blue line). This retino-thalamo-frontocortical pathway bypasses another pathway that appears to transmit ipRGC signals, and includes the master circadian oscillator (suprachiasmatic nucleus, SCN) and paraventricular thalamic nucleus (PVT). Accordingly, the new pathway has been shown to mediate a direct effect of light on mood without any circadian effects.