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Drebrin Isoforms Critically Regulate NMDAR- and mGluR-Dependent LTD Induction.

Hiroki Yasuda1,2,3, Nobuhiko Kojima1,4, Kenji Hanamura1

  • 1Department of Neurobiology and Behavior, Graduate School of Medicine, Gunma University, Maebashi, Japan.

Frontiers in Cellular Neuroscience
|October 24, 2018
PubMed
Summary

Drebrin is essential for NMDAR-dependent LTD induction in the developing brain. Its developmental switch from embryonic to adult forms prevents excessive mGluR-dependent LTD, highlighting drebrin

Keywords:
NMDAR-dependent LTDdevelopmentdrebrin isoformsknockout mousemGluR-dependent LTD

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Area of Science:

  • Neuroscience
  • Synaptic Plasticity
  • Molecular Biology

Background:

  • Drebrin is an actin-binding protein crucial for dendritic spine morphology and function.
  • Developmental expression shifts from embryonic drebrin (E) to adult drebrin (A).
  • NMDA receptor (NMDAR)-dependent long-term depression (LTD) decreases with brain maturation.

Purpose of the Study:

  • To investigate the role of drebrin in NMDAR- and mGluR-dependent LTD.
  • To elucidate how drebrin's developmental expression impacts synaptic plasticity.

Main Methods:

  • Utilized wild-type (WT), drebrin E and A double knockout (DXKO), and drebrin A knockout (DAKO) mouse models.
  • Induced LTD using low-frequency stimulation (LFS) and receptor agonists.
  • Examined NMDAR- and group 1 mGluR-dependent synaptic plasticity in developing and adult hippocampi.

Main Results:

  • Drebrin is required for NMDAR-dependent LTD induction in the developing hippocampus.
  • LFS induced robust mGluR5-dependent LTD in DAKO mice (expressing drebrin E), suggesting drebrin E promotes this plasticity.
  • Agonist-induced mGluR-dependent LTD was enhanced in DAKO mice, involving mGluR1.

Conclusions:

  • Drebrin plays a critical role in NMDAR-dependent LTD.
  • The developmental shift from drebrin E to drebrin A is crucial for preventing excessive group 1 mGluR-dependent LTD.
  • Aberrant drebrin E expression in adults may promote group 1 mGluR-dependent LTD.