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Young dentate granule cells mediate pattern separation, whereas old granule cells facilitate pattern completion.

Adult-born granule cells (GCs), a minor population of cells in the hippocampal dentate gyrus, are highly active during the first few weeks after functional integration into the neuronal network, distinguishing them from less active, older adult-born GCs and the major population of dentate GCs generated developmentally. To ascertain whether young and old GCs perform distinct memory functions, we created a transgenic mouse in which output of old GCs was specifically inhibited while leaving a substantial portion of young GCs intact. These mice exhibited enhanced or normal pattern separation between similar contexts, which was reduced following ablation of young GCs. Furthermore, these mutant mice exhibited deficits in rapid pattern completion. Therefore, pattern separation requires adult-born young GCs but not old GCs, and older GCs contribute to the rapid recall by pattern completion. Our data suggest that as adult-born GCs age, their function switches from pattern separation to rapid pattern completion.

Pubmed ID: 22365813


  • Nakashiba T
  • Cushman JD
  • Pelkey KA
  • Renaudineau S
  • Buhl DL
  • McHugh TJ
  • Rodriguez Barrera V
  • Chittajallu R
  • Iwamoto KS
  • McBain CJ
  • Fanselow MS
  • Tonegawa S



Publication Data

March 30, 2012

Associated Grants

  • Agency: NIMH NIH HHS, Id: P50 MH058880
  • Agency: NIMH NIH HHS, Id: P50 MH058880-10
  • Agency: NIMH NIH HHS, Id: P50-MH58880
  • Agency: NIMH NIH HHS, Id: R01 MH078821
  • Agency: NIMH NIH HHS, Id: R01 MH078821-17
  • Agency: NIMH NIH HHS, Id: R01-MH078821
  • Agency: NIMH NIH HHS, Id: R01-MH62122
  • Agency: NINDS NIH HHS, Id: T32 NS058280
  • Agency: Howard Hughes Medical Institute, Id:
  • Agency: Intramural NIH HHS, Id:

Mesh Terms

  • Aging
  • Animals
  • Chromosome Pairing
  • Dentate Gyrus
  • Green Fluorescent Proteins
  • Hippocampus
  • Memory
  • Mice
  • Mice, Transgenic