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BIOLOGICAL SCIENCES / NEUROSCIENCE
Paradoxical influence of hippocampal neurogenesis on working memory
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*Center for Neurobiology and Behavior and Howard Hughes Medical Institute, Columbia University, 722 West 168th Street, New York, NY 10032; and Department of Neurobiology and Brain Research Institute, University of California, Los Angeles, CA 90095
Contributed by Eric R. Kandel, January 3, 2007 (received for review December 18, 2006)
To explore the function of adult hippocampal neurogenesis, we ablated cell proliferation by using two independent and complementary methods: (i) a focal hippocampal irradiation and (ii) an inducible and reversible genetic elimination of neural progenitor cells. Previous studies using these methods found a weakening of contextual fear conditioning but no change in spatial reference memory, suggesting a supportive role for neurogenesis in some, but not all, hippocampal-dependent memory tasks. In the present study, we examined hippocampal-dependent and -independent working memory using different radial maze tasks. Surprisingly, ablating neurogenesis caused an improvement of hippocampal-dependent working memory when repetitive information was presented in a single day. These findings suggest that adult-born cells in the dentate gyrus have different, and in some cases, opposite roles in distinct types of memory.
hippocampus | irradiation | radial maze | interference
Author contributions: M.D.S. and G.M. contributed equally to this work; M.D.S. and G.M. designed research; M.D.S., G.M., S.V., I.M., and A.D.G. performed research; M.D.S. and M.V.S. contributed new reagents/analytic tools; M.D.S., G.M., S.V., and I.M. analyzed data; and M.D.S., G.M., E.R.K., and R.H. wrote the paper.
Conflict of interest statement: E.R.K. declares a conflict of interest (such as defined by PNAS policy). E.R.K. is one of four founders of Memory Pharmaceuticals and is Chairman of its Scientific Advisory Board. Memory Pharmaceuticals is concerned with developing drugs for age-related memory loss. Some of these drugs are also potentially useful in depression and schizophrenia. E.R.K.'s own laboratory is not involved in developing these drugs. E.R.K. is also a consultant for BrainCells, Inc., which works on neurogenesis, an area in which he is not directly involved.
This article contains supporting information online at www.pnas.org/cgi/content/full/0611718104/DC1.
To whom correspondence may be addressed. E-mail: erk5{at}columbia.edu or rh95{at}columbia.edu
© 2007 by The National Academy of Sciences of the USA
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