Zinc is Required for the Enhancement of Adult Hippocampal Neurogenesis
Jacqueline M. Boon1, Michael J. Chrusch4, Simon C. Spanswick1, Jo Anne Stratton3, Prajay T. Shah3, Haley Vecchiarelli4, Payal Patel1, Jeff Biernaskie3, Michael N. Hill2, Richard H. Dyck1,2
Departments of 1 Psychology, 2 Cell Biology & Anatomy, 3 Comparative Biology & Experimental Medicine, 4 Neuroscience ; all are members of the Hotchkiss Brain Institute, University of Calgary
In adult hippocampal neurogenesis (AHN), newly formed cells migrate into the granule cell layer of the dentate gyrus where they express neuronal markers, elaborate axons, make functional synaptic connections, and improve hippocampal-dependent behaviours. The level of AHN can be modulated by a variety of factors – it is increased by exercise, environmental enrichment and exposure to selective serotonin reuptake inhibitors (SSRIs); and decreased by stress and ageing. We examine whether synaptic zinc is essential for the modulation of AHN by environmental enrichment, SSRIs, and stress in normal mice (ZnT3-wildtype, WT) compared to mice lacking synaptic zinc (ZnT3-knockout, KO). We found that environmental enrichment- and SSRI-induced increases in AHN, and consequent improvements in hippocampal-dependent behavioural tasks were ablated in ZnT3-KO mice. We also examined ZnT3-WT and -KO mice that were chronically exposed to fluoxetine, while in stressed or non-stressed conditions. We found that synaptic zinc is necessary for fluoxetine-induced increases in AHN, in both stressed and non-stressed mice, but not for stress-induced decreases in AHN. The behavioural benefits associated with increases in AHN were ablated in all stressed animals, regardless of genotype. In non-stressed animals, only WT animals showed any behavioural benefits of fluoxetine treatment. These data implicate synaptic zinc as being essential for the experience-dependent enhancement of AHN, acting upstream of the effects of environmental enrichment and fluoxetine, but zinc is not necessary for the stress-induced suppression of AHN.
About the Speaker…
Dr. Richard Dyck’s research is directed to understanding the mechanisms that direct the development and plasticity of the cerebral cortex. He is particularly interested in identifying how experiences, such as activation of sensory inputs, learning, exposure to drugs/hormones and brain injury, modify cortical cells and circuits. His interest in this area of research was stimulated while an undergraduate student at the University of Lethbridge, was fostered and honed through his M.Sc. and Ph.D. training in the Neuroscience graduate program at the University of British Columbia, and through his postdoctoral tenure at The Salk Institute for Biological Studies. Dr. Dyck began his independent research career in the Department of Psychology, at the University of Calgary in 1998 and was promoted to Full Professor in 2005. His research program has been continuously supported by internal and external funding sources, including the Natural Sciences and Engineering Research Council of Canada and the Canadian Institutes for Health Research.
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