title: Removing zinc from synaptic vesicles does not impair spatial learning, memory, or sensorimotor functions in the mouse.
abstract: Zinc-enriched (ZEN) neurons are distributed widely throughout the brain and spinal cord. Synaptic vesicle zinc in these neurons is thought to function as a neuromodulator upon its release into the synaptic cleft. Consistent with this possibility, zinc or zinc chelators can alter spatial learning, working memory, and nociception in rodents. Here we use zinc transporter-3 (ZnT3) knockout mice, which are depleted of synaptic vesicle zinc, to assess the consequences of removing this potential neuromodulator on the behavior of adult mice. ZnT3 knockout mice performed equally as well as wild-type mice in the rotarod, pole, and cagetop tests of motor coordination. They exhibited normal thermal nociception in the hot-plate and tail-flick tests, and had similar olfactory, auditory and sensorimotor gating capabilities as wild-type mice. ZnT3 knockout mice behaved similarly as wild-type mice in the open field test and in the elevated plus maze test of anxiety. They exhibited normal learning and memory in the passive avoidance, Morris water maze, and fear conditioning tasks, and normal working and reference memory in a water version of the radial arm maze. We conclude that synaptic vesicle zinc is not essential for mice to be able to perform these tasks, despite the abundance of ZEN neurons in the relevant regions of the CNS. Either the neuromodulatory effects of zinc are not relevant for the tasks tested here, or mice are able to compensate easily for the absence of synaptic vesicle zinc.
authors.affiliation: Department of Biochemistry and Howard Hughes Medical Institute, University of Washington, Box 357370, Seattle, WA 98195, USA.
authors.forename: T B
authors.initials: TB
authors.lastname: Cole
authors.forename: A
authors.initials: A
authors.lastname: Martyanova
authors.forename: R D
authors.initials: RD
authors.lastname: Palmiter
mesh_terms: D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism*; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D006309:Hearing / Q000502:physiology; D007858:Learning / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009068:Movement / Q000502:physiology*; D009619:Nociceptors / Q000502:physiology; D011597:Psychomotor Performance / Q000502:physiology*; D012903:Smell / Q000502:physiology; D013028:Space Perception / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism*; D015032:Zinc / Q000172:deficiency*
chemical_list: D002352:Carrier Proteins; C017800:zinc-binding protein; D015032:Zinc