title: MS imaging and mass spectrometric synaptosome profiling identify PEP-19/pcp4 as a synaptic molecule involved in spatial learning in mice.
abstract: The Morris water maze (MWM) spatial learning task has been demonstrated to involve a cognitive switch of action control to serve the transition from an early towards a late learning phase. However, the molecular mechanisms governing this switch are largely unknown. We employed MALDI MS imaging (MSI) to screen for changes in expression of small proteins in brain structures implicated in the different learning phases. We compared mice trained for 3days and 30days in the MWM, reflecting an early and a late learning phase in relation to the acquisition of a spatial learning task. An ion with m/z of 6724, identified as PEP-19/pcp4 by top-down tandem MS, was detected at higher intensity in the dorsal striatum of the late learning phase group compared with the early learning phase group. In addition, mass spectrometric analysis of synaptosomes confirmed the presence of PEP-19/pcp4 at the synapse. PEP-19/pcp4 has previously been identified as a critical determinant of synaptic plasticity in locomotor learning. Our findings extend PEP-19/pcp4 function to spatial learning in the forebrain and put MSI forward as a valid and unbiased research strategy for the discovery and identification of the molecular machinery involved in learning, memory and synaptic plasticity. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann.
authors.affiliation: KU Leuven, Department of Biology, Laboratory of Neuroplasticity and Neuroproteomics, Naamsestraat 59, 3000 Leuven, Belgium.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Aerts
authors.affiliation: KU Leuven, Department of Biology, Laboratory of Neuroplasticity and Neuroproteomics, Naamsestraat 59, 3000 Leuven, Belgium.
authors.forename: Annelies
authors.initials: A
authors.lastname: Laeremans
authors.affiliation: KU Leuven, Department of Biology, Laboratory of Neuroplasticity and Neuroproteomics, Naamsestraat 59, 3000 Leuven, Belgium.
authors.forename: Laurens
authors.initials: L
authors.lastname: Minerva
authors.affiliation: KU Leuven, Department of Biology, Laboratory of Functional Genomics and Proteomics, Naamsestraat 59, 3000 Leuven, Belgium.
authors.forename: Kurt
authors.initials: K
authors.lastname: Boonen
authors.affiliation: Center for Proteomics, UAntwerp, Antwerp, Belgium.
authors.forename: Budamgunta
authors.initials: B
authors.lastname: Harshavardhan
authors.affiliation: KU Leuven, Laboratory of Biological Psychology, Tiensestraat 102, 3000 Leuven, Belgium.
authors.forename: Rudi
authors.initials: R
authors.lastname: D'hooge
authors.affiliation: Center for Proteomics, UAntwerp, Antwerp, Belgium; Unit Environmental Risk & Health, VITO, Mol, Belgium.
authors.forename: Dirk
authors.initials: D
authors.lastname: Valkenborg
authors.affiliation: Center for Proteomics, UAntwerp, Antwerp, Belgium; Unit Environmental Risk & Health, VITO, Mol, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Baggerman
authors.affiliation: KU Leuven, Department of Biology, Laboratory of Neuroplasticity and Neuroproteomics, Naamsestraat 59, 3000 Leuven, Belgium. Electronic address: Lut.Arckens@kuleuven.be.
authors.forename: Lutgarde
authors.initials: L
authors.lastname: Arckens
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000502:physiology; D005260:Female; D007859:Learning Disabilities / Q000378:metabolism / Q000473:pathology; D008124:Locomotion / Q000502:physiology; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology; D065853:Spatial Learning / Q000502:physiology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D013569:Synapses / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; C489091:Pcp4 protein, mouse
keywords: HPLC; MALDI; Mouse; Striatum; Synaptosome