title: CA3 NMDA receptors are crucial for rapid and automatic representation of context memory.
abstract: 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.
authors.affiliation: Unit on Genetics of Cognition and Behaviour, Mood and Anxiety Disorders Research Program, National Institute of Mental Health, Bethesda, MD 20892-3710, USA.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Cravens
authors.forename: Noelia
authors.initials: N
authors.lastname: Vargas-Pinto
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Christian
authors.forename: Kazu
authors.initials: K
authors.lastname: Nakazawa
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal; D003214:Conditioning, Classical / Q000502:physiology; D004192:Discrimination, Psychological / Q000502:physiology*; D004597:Electroshock / Q000009:adverse effects; D005239:Fear; D046352:Freezing Reaction, Cataleptic / Q000502:physiology / Q000528:radiation effects; D006624:Hippocampus / Q000378:metabolism*; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011930:Reaction Time / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate