Mitogen-activated protein kinase phosphatase-2 deletion impairs synaptic plasticity and hippocampal-dependent memory

Nor Zaihana Binti Abdul Rahman, Sam M. Greenwood, Ros R. Brett, Kyoko Tossell, Mark A. Ungless, Robin Plevin, Trevor J. Bushell

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Mitogen-activated protein kinases (MAPKs) regulate brain function and their dysfunction is implicated in a number of brain disorders, including Alzheimer’s disease. Thus there is great interest in understanding the signalling systems that control MAPK function. One family of proteins that contribute to this process, the mitogen-activated protein kinase phosphatases (MKPs), directly inactivate MAPKs through dephosphorylation. Recent studies have identified novel functions of MKPs in development, the immune system and cancer. However, a significant gap in our knowledge remains in relation to their role in brain functioning. Here, using transgenic mice where the Dusp4 gene encoding MKP-2 has been knocked out (MKP-2-/- mice), we show that long-term potentiation (LTP) is impaired in MKP-2-/- mice compared to MKP-2+/+ controls whereas neuronal excitability, evoked synaptic transmission and paired-pulse facilitation remain unaltered. Furthermore, spontaneous excitatory postsynaptic currents (sEPSC) frequency was increased in acute slices and primary hippocampal cultures prepared from MKP-2-/- mice with no effect on EPSC amplitude observed. An increase in synapse number was evident in primary hippocampal cultures which may account for the increase in spontaneous EPSC frequency. In addition no change in ERK activity was detected in both brain tissue and primary hippocampal cultures, suggesting that the effects of MKP-2 deletion were MAPK independent. Consistent with these alterations in hippocampal function, MKP-2-/- mice show deficits in spatial reference and working memory when investigated using the Morris water maze. These data show that MKP-2 plays a role in regulating hippocampal function and that this effect may be independent of MAPK signalling.
LanguageEnglish
Pages2348-2354
Number of pages6
JournalJournal of Neuroscience
Volume36
Issue number8
DOIs
Publication statusPublished - 24 Feb 2016

Fingerprint

Mitogen-Activated Protein Kinase Phosphatases
Protein Phosphatase 2
Neuronal Plasticity
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinases
Brain
Long-Term Potentiation
Excitatory Postsynaptic Potentials
Brain Diseases
Short-Term Memory
Synaptic Transmission
Synapses
Transgenic Mice
Immune System
Alzheimer Disease

Keywords

  • MKP-2
  • deletion
  • hippocampus
  • synaptic transmission
  • synaptic plasticity
  • learning and memory
  • sEPSC

Cite this

Abdul Rahman, Nor Zaihana Binti ; Greenwood, Sam M. ; Brett, Ros R. ; Tossell, Kyoko ; Ungless, Mark A. ; Plevin, Robin ; Bushell, Trevor J. / Mitogen-activated protein kinase phosphatase-2 deletion impairs synaptic plasticity and hippocampal-dependent memory. In: Journal of Neuroscience. 2016 ; Vol. 36, No. 8. pp. 2348-2354.
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Mitogen-activated protein kinase phosphatase-2 deletion impairs synaptic plasticity and hippocampal-dependent memory. / Abdul Rahman, Nor Zaihana Binti; Greenwood, Sam M.; Brett, Ros R.; Tossell, Kyoko; Ungless, Mark A.; Plevin, Robin; Bushell, Trevor J.

In: Journal of Neuroscience, Vol. 36, No. 8, 24.02.2016, p. 2348-2354.

Research output: Contribution to journalArticle

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AU - Greenwood, Sam M.

AU - Brett, Ros R.

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AU - Ungless, Mark A.

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