Hippocampal Protein-Protein Interactions in Spatial Memory

Hippocampus. 2004;14(1):46-57. doi: 10.1002/hipo.10152.


Memory consolidation in mammalian brain is accompanied by widespread reorganization of synaptic contacts and dendritic structure. Understanding of the protein-protein interactions that underlie these structural changes has been hampered by the difficulty of studying protein-protein interactions produced in vivo by signaling, learning, and other physiological responses using current methodologies. Using a novel technique that separates interacting proteins from noninteracting proteins on the basis of their protein-target affinity, we identified 16 proteins for which protein-target binding is altered in vivo by spatial learning, including stathmin, complexin I, 14-3-3, and several structural proteins including F-actin capping protein, tubulin, GFAP, and actin. Interactions between complexin and its targets (p25alpha and Drac1-like protein) and the interaction between CapZ and tubulin were calcium-dependent. The preponderance of structural proteins and proteins involved in synapse formation and reorganization of growth cones among proteins undergoing memory-specific changes in protein-protein interactions suggests that synaptic structural reorganization is a predominant feature of the consolidation phase of memory.

MeSH terms

  • Adaptor Proteins, Vesicular Transport
  • Animals
  • Blotting, Western
  • Calcium-Binding Proteins / metabolism
  • Cytoskeletal Proteins / metabolism
  • Growth Cones / metabolism
  • Hippocampus / cytology
  • Hippocampus / growth & development*
  • Hippocampus / metabolism*
  • Mass Spectrometry
  • Memory / physiology*
  • Microtubule Proteins*
  • Nerve Tissue Proteins / metabolism*
  • Neurochemistry / methods
  • Neuronal Plasticity / physiology*
  • Phosphoproteins / metabolism
  • Presynaptic Terminals / metabolism
  • Presynaptic Terminals / ultrastructure
  • Protein Binding / physiology
  • Rats
  • Space Perception / physiology*
  • Stathmin


  • Adaptor Proteins, Vesicular Transport
  • Calcium-Binding Proteins
  • Cytoskeletal Proteins
  • Microtubule Proteins
  • Nerve Tissue Proteins
  • Phosphoproteins
  • Stathmin
  • complexin I