title: Fornix deep brain stimulation induced long-term spatial memory independent of hippocampal neurogenesis.
abstract: Deep brain stimulation (DBS) is an established symptomatic treatment modality for movement disorders and constitutes an emerging therapeutic approach for the treatment of memory impairment. In line with this, fornix DBS has shown to ameliorate cognitive decline associated with dementia. Nonetheless, mechanisms mediating clinical effects in demented patients or patients with other neurological disorders are largely unknown. There is evidence that DBS is able to modulate neurophysiological activity in targeted brain regions. We therefore hypothesized that DBS might be able to influence cognitive function via activity-dependent regulation of hippocampal neurogenesis. Using stimulation parameters, which were validated to restore memory loss in a previous behavioral study, we here assessed long-term effects of fornix DBS. To do so, we injected the thymidine analog, 5-bromo-2'-deoxyuridine (BrdU), after DBS and perfused the animals 6.5 weeks later. A week prior to perfusion, memory performance was assessed in the water maze. We found that acute stimulation of the fornix improved spatial memory performance in the water maze when the probe trial was performed 1 h after the last training session. However, no evidence for stimulation-induced neurogenesis was found in fornix DBS rats when compared to sham. Our results suggest that fornix DBS improves memory functions independent of hippocampal neurogenesis, possibly through other mechanisms such as synaptic plasticity and acute neurotransmitter release.
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, 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.|Department of Neurosurgery, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.|European Graduate School of Neuroscience (Euron), Maastricht, The Netherlands.
authors.forename: Yasin
authors.initials: Y
authors.lastname: Temel
authors.affiliation: Department of Neuroscience, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.|Department of Neurology, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.|European Graduate School of Neuroscience (Euron), Maastricht, The Netherlands.
authors.forename: Sandra
authors.initials: S
authors.lastname: Schipper
authors.affiliation: Department of Neuroscience, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.|European Graduate School of Neuroscience (Euron), Maastricht, The Netherlands.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Lagiere
authors.affiliation: Department of Neuroscience, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.|Department of Morphology, Biomedical Research Institute (BIOMED), Hasselt University, Hasselt, Belgium.|European Graduate School of Neuroscience (Euron), Maastricht, The Netherlands.
authors.forename: Lisa-Maria
authors.initials: LM
authors.lastname: Schönfeld
authors.affiliation: Department of Neuropsychology and Psychopharmacology, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.|European Graduate School of Neuroscience (Euron), Maastricht, The Netherlands.
authors.forename: Arjan
authors.initials: A
authors.lastname: Blokland
authors.affiliation: Department of Neuroscience, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.|European Graduate School of Neuroscience (Euron), Maastricht, The Netherlands.
authors.forename: Ali
authors.initials: A
authors.lastname: Jahanshahi
mesh_terms: D000818:Animals; D002452:Cell Count; D004558:Electric Stimulation; D020712:Fornix, Brain / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D018782:Maze Learning / Q000502:physiology; D057567:Memory, Long-Term / Q000502:physiology*; D055495:Neurogenesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D065852:Spatial Memory / Q000502:physiology*
keywords: Deep brain stimulation; Fornix; Hippocampus; Memory; Neurogenesis
references.citation: Synapse. 2007 Apr;61(4):221-30
references.pmid: 17230550
references.citation: Neurosurgery. 2010 Oct;67(4):1073-9; discussion1080
references.pmid: 20881571
references.citation: Ann Neurol. 2008 Jan;63(1):119-23
references.pmid: 18232017
references.citation: Acta Neurochir Suppl (Wien). 1991;52:109-11
references.pmid: 1792949
references.citation: J Comp Neurol. 2011 Jan 1;519(1):6-20
references.pmid: 21120924
references.citation: Neuroscience. 2013 May 15;238:71-81
references.pmid: 23403175
references.citation: Lancet. 1991 Feb 16;337(8738):403-6
references.pmid: 1671433
references.citation: Nat Rev Neurosci. 2010 May;11(5):339-50
references.pmid: 20354534
references.citation: Brain Stimul. 2015 Nov-Dec;8(6):1058-64
references.pmid: 26321354
references.citation: Ann Neurol. 2010 Oct;68(4):521-34
references.pmid: 20687206
references.citation: Proc Natl Acad Sci U S A. 2011 Mar 29;108(13):5437-42
references.pmid: 21402918
references.citation: Brain Struct Funct. 2016 Nov;221(8):4281-4286
references.pmid: 26597361
references.citation: Hippocampus. 2015 Nov;25(11):1472-9
references.pmid: 25913775
references.citation: Neurobiol Aging. 2005 Jun;26(6):939-46
references.pmid: 15718053
references.citation: J Neurosurg. 2008 Jan;108(1):132-8
references.pmid: 18173322
references.citation: J Neurosci. 2011 Sep 21;31(38):13469-84
references.pmid: 21940440
references.citation: J Alzheimers Dis. 2013;34(1):315-23
references.pmid: 23168448
references.citation: Int Rev Neurobiol. 2012;107:283-314
references.pmid: 23206687
references.citation: Brain Stimul. 2013 Jan;6(1):72-7
references.pmid: 22405739
references.citation: Annu Rev Neurosci. 2011;34:289-307
references.pmid: 21692660
references.citation: Neuromodulation. 2006 Oct;9(4):253-61
references.pmid: 22151759
references.citation: J Chem Neuroanat. 2000 Oct;20(1):93-114
references.pmid: 11074347
references.citation: Brain Stimul. 2015 May-Jun;8(3):645-54
references.pmid: 25814404
references.citation: Cell Stem Cell. 2008 Sep 11;3(3):253-8
references.pmid: 18786413