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Post-translational synaptic protein modification as substrate for long-lasting, remote memory: an initial test.

Matthew R Holahan1, Aryeh Routtenberg

  • 1Department of Psychology, Institute for Neuroscience, Northwestern University, Evanston, Illinois 60208, USA. matthew_holahan@carleton.ca

Hippocampus
|November 18, 2006
PubMed
Summary
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Post-translational modification (PTM) of brain proteins is crucial for memory storage. Inhibiting serine/threonine kinase activity disrupts long-lasting memory, supporting the PTM model of memory formation.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cognitive Science

Background:

  • Current models suggest protein synthesis is key for long-lasting memory.
  • An alternative hypothesis proposes post-translational modification (PTM) of synaptic proteins is critical for memory.
  • This study investigates the role of PTM in long-lasting memory.

Purpose of the Study:

  • To test the hypothesis that PTM is essential for long-lasting memory.
  • To investigate the role of serine/threonine kinase activity in memory retention and extinction.

Main Methods:

  • Rats received bilateral anterior cingulate cortex infusions of a serine/threonine kinase inhibitor (H-7) before a 3-week contextual fear conditioning retention test.
  • Mice received medial prefrontal cortex injections of H-7 during extinction of a 21-day remote memory.

Related Experiment Videos

  • Behavioral performance was assessed by freezing behavior.

    • Main Results:

    • H-7 administration significantly blocked 21-day memory retention in rats.
    • H-7 administration blocked fear extinction in mice, indicating impaired remote memory.
    • Observed effects were specific to memory processes, not general behavioral impairment.

    Conclusions:

    • This study provides the first evidence that inhibiting serine/threonine kinase activity interferes with long-lasting memory.
    • Findings support the model that PTM of synaptic proteins is a critical instructive mechanism for memory storage.
    • PTM inhibition impacts both memory consolidation and extinction of remote memories.