Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus.
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.
Saxe
Michael D
MD
Center For Neurobiology and Behavior, Columbia University, New York, NY 10032, USA.
Battaglia
Fortunato
F
Wang
Jing-Wen
JW
Malleret
Gael
G
David
Denis J
DJ
Monckton
James E
JE
Garcia
A Denise R
AD
Sofroniew
Michael V
MV
Kandel
Eric R
ER
Santarelli
Luca
L
Hen
René
R
Drew
Michael R
MR
D000818:Animals; D003213:Conditioning, Psychological; D004594:Electrophysiology; D005239:Fear / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D008568:Memory; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism
D005904:Glial Fibrillary Acidic Protein; D013937:Thymidine Kinase