NT-3 facilitates hippocampal plasticity and learning and memory by regulating neurogenesis.
In the adult brain, the expression of NT-3 is largely confined to the hippocampal dentate gyrus (DG), an area exhibiting significant neurogenesis. Using a conditional mutant line in which the NT-3 gene is deleted in the brain, we investigated the role of NT-3 in adult neurogenesis, hippocampal plasticity, and memory. Bromodeoxyuridine (BrdU)-labeling experiments demonstrated that differentiation, rather than proliferation, of the neuronal precursor cells (NPCs) was significantly impaired in DG lacking NT-3. Triple labeling for BrdU, the neuronal marker NeuN, and the glial marker GFAP indicated that NT-3 affects the number of newly differentiated neurons, but not glia, in DG. Field recordings revealed a selective impairment in long-term potentiation (LTP) in the lateral, but not medial perforant path-granule neuron synapses. In parallel, the NT-3 mutant mice exhibited deficits in spatial memory tasks. In addition to identifying a novel role for NT-3 in adult NPC differentiation in vivo, our study provides a potential link between neurogenesis, dentate LTP, and spatial memory.
Shimazu
Kazuhiro
K
Section on Neural Development and Plasticity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Zhao
Mingrui
M
Sakata
Kazuko
K
Akbarian
Schahram
S
Bates
Brian
B
Jaenisch
Rudolf
R
Lu
Bai
B
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism*; D004193:Discrimination Learning / Q000502:physiology; D005260:Female; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000235:genetics / Q000378:metabolism*; D019580:Perforant Pathway / Q000166:cytology / Q000378:metabolism; D013037:Spatial Behavior / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
D020933:Neurotrophin 3