title: Mapping the dynamics of cortical neuroplasticity of skilled motor learning using micro X-ray fluorescence and histofluorescence imaging of zinc in the rat.
abstract: Synchrotron-based X-ray fluorescence imaging (XFI) of zinc (Zn) has been recently implemented to understand the efficiency of various therapeutic interventions targeting post-stroke neuroprotection and neuroplasticity. However, it is uncertain if micro XFI can resolve neuroplasticity-induced changes. Thus, we explored if learning-associated behavioral changes would be accompanied by changes in cortical Zn concentration measured by XFI in healthy adult rats. Proficiency in a skilled reach-to-eat task during early and late stages of motor learning served as a functional measure of neuroplasticity. c-Fos protein and vesicular Zn expression were employed as indirect neuronal measures of brain plasticity. A total Zn map (20×20×30μm3resolution) generated by micro XFI failed to reflect increases in either c-Fos or vesicular Zn in the motor cortex contralateral to the trained forelimb or improved proficiency in the skilled reaching task. Remarkably, vesicular Zn increased in the late stage of motor learning along with a concurrent decrease in the number of c-fos-ip neurons relative to the early stage of motor learning. This inverse dynamics of c-fos and vesicular Zn level as the motor skill advances suggest that a qualitatively different neural population, comprised of fewer active but more efficiently connected neurons, supports a skilled action in the late versus early stage of motor learning. The lack of sensitivity of the XFI-generated Zn map to visualize the plasticity-associated changes in vesicular Zn suggests that the Zn level measured by micro XFI should not be used as a surrogate marker of neuroplasticity in response to the acquisition of skilled motor actions. Nanoscopic XFI could be explored in future as a means of imaging these subtle physiological changes.
authors.affiliation: Neuroscience Research Cluster, Saskatoon, SK, S7N 5E5, Canada; College of Pharmacy and Nutrition, Saskatoon, SK, S7N 5E5, Canada; College of Medicine, University of Saskatchewan, Saskatoon, SK, S7N 5E5, Canada. Electronic address: mariam.alaverdashvili@usask.ca.
authors.forename: Mariam
authors.initials: M
authors.lastname: Alaverdashvili
authors.affiliation: Neuroscience Research Cluster, Saskatoon, SK, S7N 5E5, Canada; College of Pharmacy and Nutrition, Saskatoon, SK, S7N 5E5, Canada.
authors.forename: Phyllis G
authors.initials: PG
authors.lastname: Paterson
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism / Q000502:physiology*; D006652:Histological Techniques / Q000379:methods*; D007858:Learning / Q000502:physiology; D008297:Male; D009048:Motor Skills / Q000502:physiology*; D059906:Neuroimaging / Q000379:methods; D009473:Neuronal Plasticity / Q000502:physiology*; D061848:Optical Imaging / Q000379:methods*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017356:Synchrotrons; D015032:Zinc / Q000378:metabolism*
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D015032:Zinc
keywords: Micro X-ray fluorescence imaging; Neural efficiency; Neural plasticity; Skilled motor learning; Synchrotron; Zinc