Electrophysiological and molecular effects of bilateral deep brain stimulation of the medial forebrain bundle in a rodent model of depression

F Bühning; L Miguel Telega; Y Tong; J Pereira; V A Coenen; M D Döbrössy

doi:10.1016/j.expneurol.2022.114122

Electrophysiological and molecular effects of bilateral deep brain stimulation of the medial forebrain bundle in a rodent model of depression

Exp Neurol. 2022 Sep:355:114122. doi: 10.1016/j.expneurol.2022.114122. Epub 2022 May 28.

Authors

F Bühning¹, L Miguel Telega², Y Tong², J Pereira³, V A Coenen⁴, M D Döbrössy⁵

Affiliations

¹ Lab of Stereotaxy and Interventional Neurosciences, Dept. of Stereotactic and Functional Neurosurgery, University Freiburg - Medical Center, Germany; Dept of Stereotactic and Functional Neurosurgery, University Hospital Freiburg, Germany.
² Lab of Stereotaxy and Interventional Neurosciences, Dept. of Stereotactic and Functional Neurosurgery, University Freiburg - Medical Center, Germany; Dept of Stereotactic and Functional Neurosurgery, University Hospital Freiburg, Germany; Faculty of Biology, University of Freiburg, Germany.
³ Dept of Stereotactic and Functional Neurosurgery, University Hospital Freiburg, Germany; Brain-State Decoding Lab, Dept. of Computer Science, University of Freiburg, Germany.
⁴ Lab of Stereotaxy and Interventional Neurosciences, Dept. of Stereotactic and Functional Neurosurgery, University Freiburg - Medical Center, Germany; Dept of Stereotactic and Functional Neurosurgery, University Hospital Freiburg, Germany; Faculty of Medicine, University of Freiburg, Faculty of Medicine, Germany; Center for Basics in Neuromodulation, University of Freiburg, Germany.
⁵ Lab of Stereotaxy and Interventional Neurosciences, Dept. of Stereotactic and Functional Neurosurgery, University Freiburg - Medical Center, Germany; Dept of Stereotactic and Functional Neurosurgery, University Hospital Freiburg, Germany; Faculty of Biology, University of Freiburg, Germany. Electronic address: mate.dobrossy@uniklinik-freiburg.de.

PMID: 35636499
DOI: 10.1016/j.expneurol.2022.114122

Abstract

Background: Deep Brain Stimulation (DBS) of the Medial Forebrain Bundle (MFB) induces antidepressant effects both clinically and pre-clinically. However, the acute electrophysiological changes induced by MFB DBS remain unknown.

Objective: The study investigated acute mfb DBS effects on neuronal oscillations in distinct neuronal populations implicated in the pathophysiology of depression.

Methods: The Flinders Sensitive Line (FSL) rodent depression model and Sprague-Dawley (SD) controls were used in the study. Recording electrodes were implanted unilaterally in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), ventral tegmental area (VTA); DBS electrodes were implanted bilaterally in the mfb. The FSL Stim and SD Stim received bilateral mfb DBS, whereas the FSL Sham and SD Shams were not stimulated. Local field potentials (LFPs) from all areas were recorded at baseline, during, and post stimulation. Neuronal oscillations were analyzed.

Results: mfb DBS induced 1) a significant increase of low gamma (30-45 Hz) oscillations in the mPFC uniquely in FSLs; 2) a significant increase of low gamma oscillations in the NAc and VTA in SDs and FSLs; and 3) an increase in the expression of Gad1 in the mPFC of FSL and SDs, while only increasing the expression in the NAc of FSLs.

Conclusion: mfb DBS differentially affected neuronal oscillations in the mPFC, NAc and VTA across SD and FSL rats. Low gamma oscillations rose significantly in the mPFC of FSL rats. Molecular analysis points to a mechanism involving GABAergic interneurons as they regulate low gamma oscillations.

Keywords: Brain waves; Deep brain stimulation; Depression; Electrophysiology; Medial forebrain bundle; Rodent model.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Deep Brain Stimulation*
Depression / therapy
Medial Forebrain Bundle* / metabolism
Rats
Rats, Sprague-Dawley
Rodentia