title: Mice with deficient BK channel function show impaired prepulse inhibition and spatial learning, but normal working and spatial reference memory.
abstract: Genetic variations in the large-conductance, voltage- and calcium activated potassium channels (BK channels) have been recently implicated in mental retardation, autism and schizophrenia which all come along with severe cognitive impairments. In the present study we investigate the effects of functional BK channel deletion on cognition using a genetic mouse model with a knock-out of the gene for the pore forming α-subunit of the channel. We tested the F1 generation of a hybrid SV129/C57BL6 mouse line in which the slo1 gene was deleted in both parent strains. We first evaluated hearing and motor function to establish the suitability of this model for cognitive testing. Auditory brain stem responses to click stimuli showed no threshold differences between knockout mice and their wild-type littermates. Despite of muscular tremor, reduced grip force, and impaired gait, knockout mice exhibited normal locomotion. These findings allowed for testing of sensorimotor gating using the acoustic startle reflex, as well as of working memory, spatial learning and memory in the Y-maze and the Morris water maze, respectively. Prepulse inhibition on the first day of testing was normal, but the knockout mice did not improve over the days of testing as their wild-type littermates did. Spontaneous alternation in the y-maze was normal as well, suggesting that the BK channel knock-out does not impair working memory. In the Morris water maze knock-out mice showed significantly slower acquisition of the task, but normal memory once the task was learned. Thus, we propose a crucial role of the BK channels in learning, but not in memory storage or recollection.
authors.affiliation: Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
authors.forename: Marei
authors.initials: M
authors.lastname: Typlt
authors.forename: Magdalena
authors.initials: M
authors.lastname: Mirkowski
authors.forename: Erin
authors.initials: E
authors.lastname: Azzopardi
authors.forename: Lukas
authors.initials: L
authors.lastname: Ruettiger
authors.forename: Peter
authors.initials: P
authors.lastname: Ruth
authors.forename: Susanne
authors.initials: S
authors.lastname: Schmid
mesh_terms: D000818:Animals; D001307:Auditory Perception; D005260:Female; D005684:Gait; D006309:Hearing; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000172:deficiency* / Q000235:genetics; D008297:Male; D018782:Maze Learning; D008568:Memory; D008570:Memory, Short-Term; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels