Distinct and simultaneously active plasticity mechanisms in mouse hippocampus during different phases of Morris water maze training

Annelies Laeremans, Victor Sabanov, Tariq Ahmed, Julie Nys, Babs Van de Plas, Kasper Vinken, Daniel G. Woolley, Ilse Gantois, Rudi D’Hooge, Lutgarde Arckens, Detlef Balschun

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16 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1273-1290
Number of pages18
JournalBrain structure & function
Issue number3
Publication statusPublished - 2015
Externally publishedYes


ASJC Scopus subject areas

  • Anatomy
  • Neuroscience(all)
  • Histology

Cite this

Laeremans, A., Sabanov, V., Ahmed, T., Nys, J., Van de Plas, B., Vinken, K., Woolley, D. G., Gantois, I., D’Hooge, R., Arckens, L., & Balschun, D. (2015). Distinct and simultaneously active plasticity mechanisms in mouse hippocampus during different phases of Morris water maze training. Brain structure & function, 220(3), 1273-1290. https://doi.org/10.1007/s00429-014-0722-z