CA3 NMDA receptors are crucial for rapid and automatic representation of context memory

Eur J Neurosci. 2006 Sep;24(6):1771-80. doi: 10.1111/j.1460-9568.2006.05044.x.


It is argued that the hippocampus contributes to acquisition of context-specific memory although neural mechanisms have not been clarified. To evaluate the role of CA3 in context-specific memory, we developed one-trial context discrimination tasks to test acquisition and retrieval of contextual memory in CA3 pyramidal cell-restricted N-methyl-d-aspartate (NMDA) receptor knockout mice. Mutants were unable to discriminate conditioned and no-shock contexts 3 h after one-trial avoidance training. These phenotypes were not evident 24 h after one-trial training or 3 h after multi-trial training. Following one-trial contextual fear conditioning, mutants showed a selective deficit in context discrimination during a retention test 3 h after acquisition, although overall freezing levels were similar to those of the control mice. As in the avoidance task, this context discrimination impairment was not observed 24 h after initial conditioning. Interestingly, extending the post-shock period to 3 min during the one-trial fear conditioning task eliminated the discrimination deficit observed at the 3 h retention interval. These results suggest that: (i) impaired rapid context discrimination during the recall test is dependent on the duration of post-shock period during conditioning; (ii) CA3 NMDA receptors are critically involved in rapid and automatic formation of a unified context memory representation from the sensory information; (iii) CA3 NMDA receptors support contextual pattern separation; (iv) fear memory to foot-shock is acquired without CA3 NMDA receptors. It appears that rapid and automatic context memory representations from one-time experience are mediated, at least in part, by CA3 NMDA receptors.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Avoidance Learning / physiology
  • Behavior, Animal
  • Conditioning, Classical / physiology
  • Discrimination, Psychological / physiology*
  • Electroshock / adverse effects
  • Fear
  • Freezing Reaction, Cataleptic / physiology
  • Freezing Reaction, Cataleptic / radiation effects
  • Hippocampus / metabolism*
  • Memory / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Reaction Time / physiology
  • Receptors, N-Methyl-D-Aspartate / physiology*


  • Receptors, N-Methyl-D-Aspartate