Open AccessLateral habenula perturbation reduces default-mode network connectivity in a rat model of depression
Author(s) -
Christian Clemm von Hohenberg,
Wolfgang WeberFahr,
Philipp Lebhardt,
N. Ravi,
Urs Braun,
Natalia Gass,
Robert E. Becker,
Markus Sack,
Alejandro Cosa Liñán,
Martin Fungisai Gerchen,
Jonathan Reinwald,
Lars-Lennart Oettl,
Andreas MeyerLindenberg,
Barbara Vollmayr,
Wolfgang Kelsch,
Alexander Sartorius
Publication year - 2018
Publication title -
translational psychiatry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.652
H-Index - 82
ISSN - 2158-3188
DOI - 10.1038/s41398-018-0121-y
Subject(s) - default mode network , neuroscience , neuroimaging , major depressive disorder , psychology , functional magnetic resonance imaging , stimulation , transcranial magnetic stimulation , cognition
Hyperconnectivity of the default-mode network (DMN) is one of the most widely replicated neuroimaging findings in major depressive disorder (MDD). Further, there is growing evidence for a central role of the lateral habenula (LHb) in the pathophysiology of MDD. There is preliminary neuroimaging evidence linking LHb and the DMN, but no causal relationship has been shown to date. We combined optogenetics and functional magnetic resonance imaging (fMRI), to establish a causal relationship, using an animal model of treatment-resistant depression, namely Negative Cognitive State rats. First, an inhibitory light-sensitive ion channel was introduced into the LHb by viral transduction. Subsequently, laser stimulation was performed during fMRI acquisition on a 9.4 Tesla animal scanner. Neural activity and connectivity were assessed, before, during and after laser stimulation. We observed a connectivity decrease in the DMN following laser-induced LHb perturbation. Our data indicate a causal link between LHb downregulation and reduction in DMN connectivity. These findings may advance our mechanistic understanding of LHb inhibition, which had previously been identified as a promising therapeutic principle, especially for treatment-resistant depression.