title: Fornix deep brain stimulation enhances acetylcholine levels in the hippocampus.
abstract: Deep brain stimulation (DBS) of the fornix has gained interest as a potential therapy for advanced treatment-resistant dementia, yet the mechanism of action remains widely unknown. Previously, we have reported beneficial memory effects of fornix DBS in a scopolamine-induced rat model of dementia, which is dependent on various brain structures including hippocampus. To elucidate mechanisms of action of fornix DBS with regard to memory restoration, we performed c-Fos immunohistochemistry in the hippocampus. We found that fornix DBS induced a selective activation of cells in the CA1 and CA3 subfields of the dorsal hippocampus. In addition, hippocampal neurotransmitter levels were measured using microdialysis before, during and after 60 min of fornix DBS in a next experiment. We observed a substantial increase in the levels of extracellular hippocampal acetylcholine, which peaked 20 min after stimulus onset. Interestingly, hippocampal glutamate levels did not change compared to baseline. Therefore, our findings provide first experimental evidence that fornix DBS activates the hippocampus and induces the release of acetylcholine in this region.
authors.affiliation: Department of Neuroscience, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands. sarah.hescham@maastrichtuniversity.nl.|European Graduate School of Neuroscience (Euron), Maastricht University, Maastricht, The Netherlands. sarah.hescham@maastrichtuniversity.nl.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hescham
authors.affiliation: Department of Neuroscience, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.|European Graduate School of Neuroscience (Euron), Maastricht University, Maastricht, The Netherlands.
authors.forename: Ali
authors.initials: A
authors.lastname: Jahanshahi
authors.affiliation: University Department of Pharmacology, University of Oxford, Oxford, OX1 3QT, UK.
authors.forename: Judith V
authors.initials: JV
authors.lastname: Schweimer
authors.affiliation: Eli Lilly and Company Ltd., Windlesham, GU20 6PH, UK.
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Mitchell
authors.affiliation: Eli Lilly and Company Ltd., Windlesham, GU20 6PH, UK.
authors.forename: Guy
authors.initials: G
authors.lastname: Carter
authors.affiliation: Department of Neuropsychology and Psychopharmacology, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.
authors.forename: Arjan
authors.initials: A
authors.lastname: Blokland
authors.affiliation: University Department of Pharmacology, University of Oxford, Oxford, OX1 3QT, UK.
authors.forename: Trevor
authors.initials: T
authors.lastname: Sharp
authors.affiliation: Department of Neuroscience, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands. y.temel@maastrichtuniversity.nl.|Department of Neurosurgery, Maastricht University Medical Centre, PO Box 5800, 6202 AZ, Maastricht, The Netherlands. y.temel@maastrichtuniversity.nl.|European Graduate School of Neuroscience (Euron), Maastricht University, Maastricht, The Netherlands. y.temel@maastrichtuniversity.nl.
authors.forename: Yasin
authors.initials: Y
authors.lastname: Temel
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D046690:Deep Brain Stimulation; D020712:Fornix, Brain / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D018698:Glutamic Acid; D000109:Acetylcholine
keywords: Acetylcholine; Deep brain stimulation; Fornix; Hippocampus; Memory