Light augments antidepressant response via astroglial modulation of lateral habenula

Successful antidepressant treatments are still difficult to achieve. Recently, bright light stimulation (BLS) was shown effective in non-seasonal depression but its mode of action remains elusive. We demonstrate, using a new mouse model of depression resistant to antidepressants including ketamine, that both chemogenetic activation of lateral habenula (LHb) astroglia and serotonin (5-HT) depletion prevented the potentiating effect of BLS on the antidepressant response. These results show that improved behavioral outcome produced by BLS requires habenular astroglia and 5-HT tone as crucial buffer systems. Overall design: PFC mRNA profiles of 10-weeks-old naïve, stressed, and Ketamine + Scopolamine + light treated wild type mice were generated by deep sequencing, in duplicate, using Illumina.