Elsevier

Neuroscience

Volume 130, Issue 4, 2005, Pages 843-852
Neuroscience

A role for adult neurogenesis in spatial long-term memory

https://doi.org/10.1016/j.neuroscience.2004.10.009Get rights and content

Abstract

Adult hippocampal neurogenesis has been linked to learning but details of the relationship between neuronal production and memory formation remain unknown. Using low dose irradiation to inhibit adult hippocampal neurogenesis we show that new neurons aged 4–28 days old at the time of training are required for long-term memory in a spatial version of the water maze. This effect of irradiation was specific since long-term memory for a visibly cued platform remained intact. Furthermore, irradiation just before or after water maze training had no effect on learning or long-term memory. Relationships between learning and new neuron survival, as well as proliferation, were investigated but found non-significant. These results suggest a new role for adult neurogenesis in the formation and/or consolidation of long-term, hippocampus-dependent, spatial memories.

Section snippets

Animals and timeline

Six to eight male Long Evans rats (Charles River, Saint-Constant, QC, Canada) comprised each group of IRR-learners, learners, or cage controls, except the 1-week learner group in which 13 rats were used. Rats were housed on a 12 h light/dark cycle with lights on from 7:00 am to 7:00 pm. Beginning at 40 days of age rats were irradiated (IRR-learners) or sham-irradiated (learners and cage controls) to eliminate adult neurogenesis in the dentate gyrus (Monje et al., 2002). Four weeks later, when

Irradiation blocks adult neurogenesis

Irradiation has been shown to severely reduce adult hippocampal neurogenesis, while sparing the production of other cell types in the adult CNS (Monje et al., 2002). Using confocal microscopy we found that adult-born neurons dual-labeled for BrdU and CaBP (BrdU+/CaBP+) were virtually eliminated in irradiated rats but the number of adult born non-neuronal cells (BrdU+/CaBP−) was not different from sham-irradiated rats (Figs. 1B, 2). Numbers of surviving neurons at 3 and 6 weeks post-BrdU (6 and

Discussion

Here we provide evidence that adult-born dentate granule neurons may be required for the formation of long-term spatial memories in the rat. Evidence for a contribution of neurogenesis to learning and to the behavioral effects of antidepressants has been presented (Shors et al., 2001, 2002; Madsen et al., 2003; Santarelli et al., 2003; Raber et al., 2004a,b), but this is the first evidence for a specific role in long-term memory. To test whether the memory deficits described were due to the

Acknowledgments

The authors are grateful to Dr. Howard Dobson and Kim Stewart at the Guelph Veterinary Hospital for providing and assisting in the use of the irradiation source, Dr. Sabrina Wang for assisting in the irradiation procedures, Dr. Gordon Winocur for assistance with the cued test and Dr. Derek van der Kooy for helpful comments. This work was supported by the Ontario Neurotrauma Foundation (J.S.S.), CIHR (J.M.W.) and NSERC (R.J.M.).

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