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

• Verfasst von: Clemm von Hohenberg, Christian [VerfasserIn]
• Verfasst von: Meyer-Lindenberg, Andreas [VerfasserIn]
• Verfasst von: Vollmayr, Barbara [VerfasserIn]
• Verfasst von: Sartorius, Alexander [VerfasserIn]
• Titel: Lateral habenula perturbation reduces default-mode network connectivity in a rat model of depression
• Verf.angabe: Christian Clemm von Hohenberg, Wolfgang Weber-Fahr, Philipp Lebhardt, Namasivayam Ravi, Urs Braun, Natalia Gass, Robert Becker, Markus Sack, Alejandro Cosa Linan, Martin Fungisai Gerchen, Jonathan Rochus Reinwald, Lars-Lennart Oettl, Andreas Meyer-Lindenberg, Barbara Vollmayr, Wolfgang Kelsch and Alexander Sartorius
• E-Jahr: 2018
• Jahr: 27 March 2018
• Umfang: 9 S.
• Fussnoten: Gesehen am 08.04.2019
• Titel Quelle: Enthalten in: Translational Psychiatry
• Ort Quelle: London : Nature Publishing Group, 2011
• Jahr Quelle: 2018
• Band/Heft Quelle: 8(2018), Artikel-ID 68, Seite 1-9
• ISSN Quelle: 2158-3188
• DOI: doi:10.1038/s41398-018-0121-y
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Animals
• Sach-SW: Brain
• Sach-SW: Brain Mapping
• Sach-SW: Depressive Disorder, Treatment-Resistant
• Sach-SW: Disease Models, Animal
• Sach-SW: Habenula
• Sach-SW: Magnetic Resonance Imaging
• Sach-SW: Male
• Sach-SW: Neural Pathways
• Sach-SW: Optogenetics
• Sach-SW: Rats
• K10plus-PPN: 1662924291

Abstract

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.