To fear or not to fear: what was the question? A potential role for Ras-GRF in memory

Bioessays. 1998 Sep;20(9):691-5. doi: 10.1002/(SICI)1521-1878(199809)20:9<691::AID-BIES1>3.0.CO;2-K.


Learning, making memories, and forgetting are thought to require changes in the strengths of connections between neurons. Such changes in synaptic strength occur in two phases: an early phase that is likely mediated by covalent modifications to existing proteins, and a delayed phase that depends on new gene expression and protein synthesis. However, the biochemical mechanisms by which neuronal activity leads to changes in synaptic strength are poorly understood. Recently, it has been shown that animals that lack Ras guanine nucleotide releasing factor (Ras-GRF), a Ca(2+)-dependent activator of the small GTP-binding protein, Ras, do not learn fear responses normally, although other types of learning appear normal. These animals show defects in the delayed phase of memory formation within the neuronal circuit that mediates fear conditioning. This paper suggests that Ras-GRF couples synaptic activity to the molecular mechanisms that consolidate changes in synaptic strength within specific neuronal circuits.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amygdala / physiology*
  • Animals
  • Avoidance Learning / physiology*
  • Fear / physiology*
  • Geniculate Bodies / physiology
  • Guanine Nucleotide Exchange Factors
  • Humans
  • Learning Disabilities / physiopathology
  • Long-Term Potentiation / physiology*
  • Memory / physiology*
  • Memory Disorders / physiopathology
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Nerve Tissue Proteins / physiology*
  • Proteins / genetics
  • Proteins / physiology*
  • Receptors, AMPA / physiology
  • Signal Transduction
  • Thalamus / physiology
  • ras Guanine Nucleotide Exchange Factors
  • ras Proteins / physiology
  • ras-GRF1


  • Guanine Nucleotide Exchange Factors
  • Nerve Tissue Proteins
  • Proteins
  • Receptors, AMPA
  • ras Guanine Nucleotide Exchange Factors
  • ras-GRF1
  • ras Proteins