title: Distinct and simultaneously active plasticity mechanisms in mouse hippocampus during different phases of Morris water maze training.
abstract: Although the Morris water maze (MWM) is the most frequently used protocol to examine hippocampus-dependent learning in mice, not much is known about the spatio-temporal dynamics of underlying plasticity processes. Here, we studied molecular and cellular hippocampal plasticity mechanisms during early and late phases of spatial learning in the MWM. Quantitative in situ hybridization for the immediate early genes zif268 and Homer1a (H1a) revealed phase-dependent differences in their expression between areas CA1 and CA3. During the initial learning phase, CA1 expression levels of the molecular plasticity marker H1a, but not of the activity reporter gene zif268, were related to task proficiency; whereas no learning-specific changes could be detected in CA3. Simultaneously, the ratio of surface-expressed NMDAR subunits NR2A and NR2B was downregulated as measured by acute slice biotinylation assay, while the total number of surface NMDARs was unaltered. When intrinsic 'somatic' and synaptic plasticity in the CA1-region of hippocampal slices were examined, we found that early learning promotes intrinsic neuronal plasticity as manifested by a reduction of spike frequency adaptation and postburst afterhyperpolarization. At the synaptic level, however, maintenance of long-term potentiation (LTP) in all learning groups was impaired which is most likely due to 'intrinsic' learning-induced LTP which occluded any further electrically induced LTP. Late learning, in contrast, was characterized by re-normalized H1a, NR2A and NR2B expression and neuronal firing, yet a further strengthening of learning-induced LTP. Together, our data support a precisely timed cascade of complex molecular and subcellular transformations occurring from early to late MWM learning.
authors.affiliation: Laboratory of Neuroplasticity and Neuroproteomics, KU Leuven, Naamsestraat 59, 3000, Leuven, Belgium.
authors.forename: Annelies
authors.initials: A
authors.lastname: Laeremans
authors.forename: Victor
authors.initials: V
authors.lastname: Sabanov
authors.forename: Tariq
authors.initials: T
authors.lastname: Ahmed
authors.forename: Julie
authors.initials: J
authors.lastname: Nys
authors.forename: Babs
authors.initials: B
authors.lastname: Van de Plas
authors.forename: Kasper
authors.initials: K
authors.lastname: Vinken
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Woolley
authors.forename: Ilse
authors.initials: I
authors.lastname: Gantois
authors.forename: Rudi
authors.initials: R
authors.lastname: D'Hooge
authors.forename: Lutgarde
authors.initials: L
authors.lastname: Arckens
authors.forename: Detlef
authors.initials: D
authors.lastname: Balschun
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism; D056654:CA3 Region, Hippocampal / Q000378:metabolism; D015536:Down-Regulation; D051766:Early Growth Response Protein 1 / Q000235:genetics; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology*; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics; D013997:Time Factors
chemical_list: D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate