title: Electrical Stimulation Normalizes c-Fos Expression in the Deep Cerebellar Nuclei of Depressive-like Rats: Implication of Antidepressant Activity.
abstract: The electrical stimulation of specific brain targets has been shown to induce striking antidepressant effects. Despite that recent data have indicated that cerebellum is involved in emotional regulation, the mechanisms by which stimulation improved mood-related behaviors in the cerebellum remained largely obscure. Here, we investigated the stimulation effects of the ventromedial prefrontal cortex (vmPFC), nucleus accumbens (NAc), and lateral habenular nucleus on the c-Fos neuronal activity in various deep cerebellar and vestibular nuclei using the unpredictable chronic mild stress (CMS) animal model of depression. Our results showed that stressed animals had increased number of c-Fos cells in the cerebellar dentate and fastigial nuclei, as well as in the spinal vestibular nucleus. To examine the stimulation effects, we found that vmPFC stimulation significantly decreased the c-Fos activity within the cerebellar fastigial nucleus as compared to the CMS sham. Similarly, there was also a reduction of c-Fos expression in the magnocellular part of the medial vestibular nucleus in vmPFC- and NAc core-stimulated animals when compared to the CMS sham. Correlational analyses showed that the anxiety measure of home-cage emergence escape latency was positively correlated with the c-Fos neuronal activity of the cerebellar fastigial and magnocellular and parvicellular parts of the interposed nuclei in CMS vmPFC-stimulated animals. Interestingly, there was a strong correlation among activation in these cerebellar nuclei, indicating that the antidepressant-like behaviors were possibly mediated by the vmPFC stimulation-induced remodeling within the forebrain-cerebellar neurocircuitry.
authors.affiliation: Department of Biology, University of Girona, Girona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Huguet
authors.affiliation: Department of Biology, University of Girona, Girona, Spain. elisabet.kadar@udg.edu.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Kadar
authors.affiliation: Departments of Neuroscience and Neurosurgery, Maastricht University, Maastricht, The Netherlands.
authors.forename: Yasin
authors.initials: Y
authors.lastname: Temel
authors.affiliation: School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China. limlw@hku.hk.|Department of Biological Sciences, Sunway University, Bandar Sunway, Malaysia. limlw@hku.hk.
authors.forename: Lee Wei
authors.initials: LW
authors.lastname: Lim
mesh_terms: D000818:Animals; D002529:Cerebellar Nuclei / Q000378:metabolism* / Q000473:pathology; D003866:Depressive Disorder / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D004599:Electric Stimulation Therapy; D019262:Habenula / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D058542:Implantable Neurostimulators; D008297:Male; D009714:Nucleus Accumbens / Q000378:metabolism / Q000473:pathology; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological; D035501:Uncertainty; D014726:Vestibular Nuclei / Q000378:metabolism / Q000473:pathology
chemical_list: D016760:Proto-Oncogene Proteins c-fos
keywords: Antidepressant-like behaviors; Deep cerebellar nuclei; High-frequency stimulation; Ventromedial prefrontal cortex; Vestibular nuclei