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Presynaptic Rac1 in the hippocampus selectively regulates working memory.

Jaebin Kim1, Edwin Bustamante1, Peter Sotonyi2

  • 1Department of Cell Biology, Duke University School of Medicine, Durham, United States.

Elife
|July 24, 2024
PubMed
Summary

Rac1 signaling impacts spatial working memory via presynaptic terminals and long-term memory via postsynaptic sites. This study uncovers Rac1

Keywords:
Rac1cell biologyhippocampusmouseneurosciencepresynapticshort-term plasticityworking memory

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Rac1, a small GTPase, is involved in actin remodeling and signaling.
  • Rac1 signaling influences learning, memory, and synaptic plasticity.
  • The precise roles of Rac1 in different cognitive functions and plasticity remain unclear.

Purpose of the Study:

  • To investigate the distinct roles of Rac1 in presynaptic and postsynaptic compartments.
  • To elucidate the molecular mechanisms underlying presynaptic Rac1 function in cognition.
  • To identify proteins and post-translational modifications associated with presynaptic Rac1 signaling.

Main Methods:

  • Utilized a genetically encoded Rac1 inhibitor targeted to presynaptic terminals.
  • Employed mass spectrometry to analyze the presynaptic proteomic and post-translational landscape.
  • Examined changes in synaptic vesicle distribution, morphology, and postsynaptic ultrastructure.

Main Results:

  • Presynaptic Rac1 inhibition selectively impaired spatial working memory in mice.
  • Postsynaptic Rac1 inhibition affected longer-term cognitive processes.
  • Identified serine/threonine kinases and phosphorylated proteins regulating synaptic vesicles at active presynaptic Rac1 sites.
  • Observed alterations in synaptic vesicle dynamics and postsynaptic structures.

Conclusions:

  • Rac1 signaling plays a critical, previously unrecognized, presynaptic role in cognitive processes.
  • Distinct presynaptic and postsynaptic functions of Rac1 contribute to different forms of memory and plasticity.
  • Presynaptic Rac1 regulates synaptic vesicle function, impacting cognitive performance.