title: Deep brain stimulation of the forniceal area enhances memory functions in experimental dementia: the role of stimulation parameters.
abstract: Deep brain stimulation (DBS) is currently being evaluated as a potential therapy in improving memory functions in Alzheimer's disease. The target for DBS and the stimulation parameters to be used are unknown. Here, we implanted bilateral electrodes in the vicinity of the fornix, a key element of the memory circuitry, and applied DBS with different stimulation frequencies and amplitudes in an experimental model of dementia. Rats received scopolamine, a muscarinic acetylcholine receptor antagonist, to mimic memory impairment. Rats were then tested in the object location task with the following conditions: (i) with attachment of stimulation cable (off stimulation), and (ii) with DBS at various amplitudes (50 μA, 100 μA and 200 μA), 100 μs pulse width and 100 Hz or 10 Hz stimulation frequency. DBS reversed the memory impairing effects of scopolamine when compared to sham rats. We found that the fornix is not sensitive to the frequency of stimulation, but rather to current levels. With the most optimal stimulation parameter, we found no side-effects on anxiety levels and general motor activity. These findings identify the fornix as a key region in controlling spatial memory functions. DBS of this region, using tailored stimulation parameters, has the potential to improve memory functions in conditions characterised by memory impairment.
authors.affiliation: Department of Neuroscience, Maastricht University Medical Center, Maastricht, PO Box 5800, 6202 AZ Maastricht, The Netherlands.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hescham
authors.forename: Lee Wei
authors.initials: LW
authors.lastname: Lim
authors.forename: Ali
authors.initials: A
authors.lastname: Jahanshahi
authors.forename: Harry W M
authors.initials: HW
authors.lastname: Steinbusch
authors.forename: Jos
authors.initials: J
authors.lastname: Prickaerts
authors.forename: Arjan
authors.initials: A
authors.lastname: Blokland
authors.forename: Yasin
authors.initials: Y
authors.lastname: Temel
mesh_terms: D000818:Animals; D046690:Deep Brain Stimulation / Q000379:methods*; D003704:Dementia / Q000628:therapy*; D004195:Disease Models, Animal; D004567:Electrodes, Implanted; D020712:Fornix, Brain / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013037:Spatial Behavior / Q000502:physiology