Daily changes in light influence mood via inhibitory networks within the thalamic perihabenular nucleus

Exposure to irregular lighting schedules leads to deficits in affective behaviors. The retino-recipient perihabenular nucleus (PHb) of the dorsal thalamus has been shown to mediate these effects in mice. However, the mechanisms of how light information is processed within the PHb remains unknown. Here, we show that the PHb contains a distinct cluster of GABAergic neurons that receive direct retinal input. These neurons are part of a larger inhibitory network composed of the thalamic reticular nucleus and zona incerta, known to modulate thalamocortical communication. In addition, PHb^GABA neurons locally modulate excitatory-relay neurons, which project to limbic centers. Chronic exposure to irregular light-dark cycles alters photo-responsiveness and synaptic output of PHb^GABA neurons, disrupting daily oscillations of genes associated with inhibitory and excitatory PHb signaling. Consequently, selective and chronic PHb^GABA manipulation results in mood alterations that mimic those caused by irregular light exposure. Together, light-mediated disruption of PHb inhibitory networks underlies mood deficits.