Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus

MD Saxe, F Battaglia, JW Wang… - Proceedings of the …, 2006 - National Acad Sciences
MD Saxe, F Battaglia, JW Wang, G Malleret, DJ David, JE Monckton, ADR Garcia…
Proceedings of the National Academy of Sciences, 2006National Acad Sciences
Although hippocampal neurogenesis has been described in many adult mammals, the
functional impact of this process on physiology and behavior remains unclear. In the present
study, we used two independent methods to ablate hippocampal neurogenesis and found
that each procedure caused a limited behavioral deficit and a loss of synaptic plasticity
within the dentate gyrus. Specifically, focal X irradiation of the hippocampus or genetic
ablation of glial fibrillary acidic protein-positive neural progenitor cells impaired contextual …
Although hippocampal neurogenesis has been described in many adult mammals, the functional impact of this process on physiology and behavior remains unclear. In the present study, we used two independent methods to ablate hippocampal neurogenesis and found that each procedure caused a limited behavioral deficit and a loss of synaptic plasticity within the dentate gyrus. Specifically, focal X irradiation of the hippocampus or genetic ablation of glial fibrillary acidic protein-positive neural progenitor cells impaired contextual fear conditioning but not cued conditioning. Hippocampal-dependent spatial learning tasks such as the Morris water maze and Y maze were unaffected. These findings show that adult-born neurons make a distinct contribution to some but not all hippocampal functions. In a parallel set of experiments, we show that long-term potentiation elicited in the dentate gyrus in the absence of GABA blockers requires the presence of new neurons, as it is eliminated by each of our ablation procedures. These data show that new hippocampal neurons can be preferentially recruited over mature granule cells in vitro and may provide a framework for how this small cell population can influence behavior.
National Acad Sciences