title: Programmed deep brain stimulation synchronizes VTA gamma band field potential and alleviates depressive-like behavior in rats.
abstract: Deep brain stimulation (DBS) significantly alleviates symptoms in various neurological disorders. Current research focuses on developing programmed stimulation protocols for customization to individual symptoms. However, the therapeutic mechanism of action of programmed DBS (pDBS) is poorly understood. We previously demonstrated that pDBS in the ventral tegmental area (VTA) normalizes molecular and behavioral abnormalities in the Flinders Sensitive Line (FSL) rat model for depression. Herein, we examined the effect of a short-duration, low-frequency DBS template on local field potential (LFP) synchronization patterns along the anterior-posterior axis of the VTA of FSL rats, and correlation of this effect with depressive-like behavior, as compared with non-programmed, continuous low-frequency DBS (npDBS). We used the wavelet phase coherence (WPC) measure for effective representation of time and frequency of LFP patterns, and the forced swim test to measure immobility (despair). Baseline WPC values were lower in FSLs as compared with SD controls, at the low and high gamma frequency range (above 30 Hz). Baseline immobility scores for FSL rats were higher than those of SD rats, while pDBS, and not npDBS, significantly reduced FSL immobility scores to control SD levels, up to day 14. pDBS also significantly increased the change (between baseline and day 14) in WPC values, in beta, low gamma and high gamma frequency ranges. The change in high gamma (60-100 Hz) WPC values correlated with improvement in depressive-like behavior. Our results suggest that programmed DBS of the VTA increases interaction among local neuronal populations, an effect that may underlie the normalization of depressive-like behavior.
authors.affiliation: The Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar-Ilan University, 52900, Ramat-Gan, Israel.
authors.forename: Tomer
authors.initials: T
authors.lastname: Gazit
authors.affiliation: The Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar-Ilan University, 52900, Ramat-Gan, Israel.
authors.forename: Alexander
authors.initials: A
authors.lastname: Friedman
authors.affiliation: The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 52900, Israel.
authors.forename: Elad
authors.initials: E
authors.lastname: Lax
authors.affiliation: The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 52900, Israel.
authors.forename: Merav
authors.initials: M
authors.lastname: Samuel
authors.affiliation: The Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar-Ilan University, 52900, Ramat-Gan, Israel.
authors.forename: Roy
authors.initials: R
authors.lastname: Zahut
authors.affiliation: The Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar-Ilan University, 52900, Ramat-Gan, Israel.
authors.forename: Moshe
authors.initials: M
authors.lastname: Katz
authors.affiliation: The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 52900, Israel.
authors.forename: Lital
authors.initials: L
authors.lastname: Abraham
authors.affiliation: The Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar-Ilan University, 52900, Ramat-Gan, Israel.
authors.forename: Hadass
authors.initials: H
authors.lastname: Tischler
authors.affiliation: The Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar-Ilan University, 52900, Ramat-Gan, Israel.
authors.forename: Mina
authors.initials: M
authors.lastname: Teicher
authors.affiliation: The Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar-Ilan University, 52900, Ramat-Gan, Israel; The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 52900, Israel. Electronic address: yadidg@gmail.com.
authors.forename: Gal
authors.initials: G
authors.lastname: Yadid
mesh_terms: D000818:Animals; D046690:Deep Brain Stimulation / Q000379:methods*; D003863:Depression / Q000503:physiopathology* / Q000628:therapy*; D004195:Disease Models, Animal; D065818:Gamma Rhythm; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017557:Ventral Tegmental Area / Q000503:physiopathology*
keywords: Deep brain stimulation; Depression; Gamma band synchronization; Local field potentials; Ventral tegmental area