Lateral habenula perturbation reduces default-mode network connectivity in a rat model of depression

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Zeitschriftentitel:	Translational Psychiatry
Personen und Körperschaften:	Clemm von Hohenberg, Christian, Weber-Fahr, Wolfgang, Lebhardt, Philipp, Ravi, Namasivayam, Braun, Urs, Gass, Natalia, Becker, Robert, Sack, Markus, Cosa Linan, Alejandro, Gerchen, Martin Fungisai, Reinwald, Jonathan Rochus, Oettl, Lars-Lennart, Meyer-Lindenberg, Andreas, Vollmayr, Barbara, Kelsch, Wolfgang, Sartorius, Alexander
In:	Translational Psychiatry, 8, 2018, 1
Format:	E-Article
Sprache:	Englisch
veröffentlicht:	Springer Science and Business Media LLC
Schlagwörter:	Biological Psychiatry Cellular and Molecular Neuroscience Psychiatry and Mental health

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Zusammenfassung:	<jats:title>Abstract</jats:title><jats:p>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 <jats:italic>Negative Cognitive State</jats:italic> 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.</jats:p>
ISSN:	2158-3188
DOI:	10.1038/s41398-018-0121-y