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NT-3 facilitates hippocampal plasticity and learning and memory by regulating neurogenesis

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LEARNING & MEMORY
卷 13, 期 3, 页码 307-315

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COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/lm.76006

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  1. Intramural NIH HHS Funding Source: Medline
  2. NIDA NIH HHS [K08 DA000479] Funding Source: Medline

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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.

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