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The MK2 cascade regulates mGluR-dependent synaptic plasticity and reversal learning.

Lucia Privitera1, Ellen L Hogg1, Matthias Gaestel2

  • 1(a)Bradford School of Pharmacy and Medical Sciences, University of Bradford, Bradford, BD7 1DP, United Kingdom.

Neuropharmacology
|May 27, 2019
PubMed
Summary

The p38 MAPK/MAPK-activated protein kinase 2 (MK2) cascade is crucial for cognitive flexibility. MK2 regulates synaptic plasticity, specifically long-term depression (LTD), which is vital for updating spatial memories and adapting behavior.

Keywords:
Barnes mazeHippocampusMAP kinase signallingReversal learningmGluR-LTDmGluR-mediated priming of LTP

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cognitive Science

Background:

  • Cognitive flexibility, the ability to update or erase memories, is essential for adapting behavior in changing environments.
  • This process involves balancing synaptic potentiation (memory acquisition) and synaptic depression (memory modulation).

Purpose of the Study:

  • To investigate the role of the p38 MAPK/MAPK-activated protein kinase 2 (MK2) cascade in cognitive flexibility and synaptic plasticity.
  • To determine the impact of MK2 deficiency on long-term potentiation (LTP) and long-term depression (LTD) at hippocampal CA1 synapses.

Main Methods:

  • Utilized MK2 knockout (KO) mice and wildtype littermates.
  • Assessed spatial learning and reversal learning using the Barnes maze task.
  • Electrophysiological recordings were performed to measure LTP and LTD at CA1 synapses.

Main Results:

  • MK2 KO mice exhibited impaired metabotropic glutamate receptor-dependent LTD (mGluR-LTD) but intact N-methyl-D-aspartate receptor-dependent LTD (NMDAR-LTD).
  • While LTP amplitude was unaffected, priming of LTP by group I metabotropic receptors was impaired in MK2 KO mice.
  • MK2 KO mice showed deficits in reversal learning, specifically in optimizing search strategies, despite intact initial spatial learning.

Conclusions:

  • The mGluR-p38-MK2 cascade is critical for cognitive flexibility by regulating LTD amplitude and LTP priming.
  • This pathway plays a key role in updating previously learned spatial information and adapting behavior.