Astroglia in lateral habenula is essential for antidepressant efficacy of light

Sarah Delcourte; Adeline Etiévant; Renaud Rovera; Damien Mor; Howard Michael Cooper; Hiep Dinh Le; April E. Williams; Satchidananda Panda; Rihab Azmani; Olivier Raineteau; Christine Coutanson; Ouria Dkhissi‐Benyahya; Nasser Haddjeri

doi:10.1101/2020.07.31.230201

NeurosciencebioRxivJul 31, 2020

Preprint

Astroglia in lateral habenula is essential for antidepressant efficacy of light

Sarah Delcourte iD, Adeline Etiévant iD, Renaud Rovera iD, Damien Mor iD, Howard Michael Cooper iD, Hiep Dinh Le iD, April E. Williams iD, Satchidananda Panda iD, Rihab Azmani, Olivier Raineteau iD, Christine Coutanson, Ouria Dkhissi‐Benyahya iD, Nasser Haddjeri iD

Abstract

Successful antidepressant (AD) 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 here, using a new mouse model of depression resistant to ADs including ketamine, that chemogenetic activation of lateral habenula (LHb) astroglia prevented the potentiating effect of BLS on the AD response. Additionally, the beneficial action of BLS was associated with upregulation of a specific part of the prefrontal cortex opioid system. These results show that improved behavioral outcome produced by BLS requires habenular astroglia and endogenous opioids as crucial buffer systems.

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