Shimazu Kazuhiro, Zhao Mingrui, Sakata Kazuko, Akbarian Schahram, Bates Brian, Jaenisch Rudolf, Lu Bai
Section on Neural Development and Plasticity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Learn Mem. 2006 May-Jun;13(3):307-15. doi: 10.1101/lm.76006. Epub 2006 May 16.
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.
在成人大脑中，NT-3的表达主要局限于海马齿状回（DG），该区域具有显著的神经发生。利用一种条件突变品系，其中NT-3基因在大脑中被敲除，我们研究了NT-3在成体神经发生、海马可塑性和记忆中的作用。溴脱氧尿苷（BrdU）标记实验表明，在缺乏NT-3的DG中，神经元前体细胞（NPC）的分化而非增殖受到显著损害。对BrdU、神经元标记物NeuN和胶质细胞标记物GFAP的三重标记表明，NT-3影响DG中新分化神经元的数量，但不影响胶质细胞的数量。场记录显示，外侧穿通通路-颗粒神经元突触的长时程增强（LTP）存在选择性损害，而内侧则无。同时，NT-3突变小鼠在空间记忆任务中表现出缺陷。除了确定NT-3在体内成体NPC分化中的新作用外，我们的研究还提供了神经发生、齿状回LTP和空间记忆之间的潜在联系。
