Brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) are known to regulate neuronal morphology and the formation of neural circuits, yet the neuronal targets of each neurotrophin are still to be defined. To address how these neurotrophins regulate the morphological and synaptic differentiation of developing olfactory bulb (OB) GABAergic interneurons, we analyzed the effect of BDNF and NT-3 on GABA⁺-neurons and on different subtypes of these neurons: tyrosine hydroxylase (TH⁺); calretinin (Calr⁺); calbindin (Calb⁺); and parvalbumin (PVA⁺). These cells were generated from cultured embryonic mouse olfactory bulb neural stem cells (eOBNSCs) and after 14 days in vitro (DIV), when the neurons expressed TrkB and/or TrkC receptors, BDNF and NT-3 did not significantly change the number of neurons. However, long-term BDNF treatment did produce a longer total dendrite length and/or more dendritic branches in all the interneuron populations studied, except for PVA⁺-neurons. Similarly, BDNF caused an increase in the cell body perimeter in all the interneuron populations analyzed, except for PVA⁺-neurons. GABA⁺- and TH⁺-neurons were also studied at 21 DIV, when BDNF produced significantly longer neurites with no clear change in their number. Notably, these neurons developed synaptophysin⁺ boutons at 21 DIV, the size of which augmented significantly following exposure to either BDNF or NT-3. Our results show that in conditions that maintain neuronal survival, BDNF but not NT-3 promotes the morphological differentiation of developing OB interneurons in a cell-type-specific manner. In addition, our findings suggest that BDNF and NT-3 may promote synapse maturation by enhancing the size of synaptic boutons.

已知脑源性神经营养因子 (BDNF) 和神经营养因子 3 (NT-3) 可调节神经元形态和神经回路的形成，但每种神经营养因子的神经元靶点仍有待确定。为了解决这些神经营养因子如何调节发育中的嗅球 (OB) GABA 能中间神经元的形态和突触分化，我们分析了 BDNF 和 NT-3 对 GABA ⁺ -神经元和这些神经元的不同亚型的影响：酪氨酸羟化酶 (TH ⁺ ) ; 钙调蛋白 (Calr ⁺ ); 钙结合蛋白 (Calb ⁺ ); 和小白蛋白（PVA ⁺）。这些细胞由培养的胚胎小鼠嗅球神经干细胞 (eOBNSCs) 产生，在体外 (DIV) 14 天后，当神经元表达 TrkB 和/或 TrkC 受体时，BDNF 和 NT-3 并没有显着改变神经元的数量. 然而，长期 BDNF 治疗确实在所有研究的中间神经元群体中产生了更长的总树突长度和/或更多的树突分支，PVA ⁺ -神经元除外。^{类似地，BDNF 导致所分析的所有中间神经元群体的细胞体周长增加，PVA +} -神经元除外。GABA ⁺ - 和 TH ⁺- 神经元也在 21 DIV 进行了研究，当时 BDNF 产生明显更长的神经突，其数量没有明显变化。值得注意的是，这些神经元在 21 DIV 时产生了突触素⁺ boutons，其大小在暴露于 BDNF 或 NT-3 后显着增加。我们的研究结果表明，在维持神经元存活的条件下，BDNF 而不是 NT-3 以细胞类型特异性方式促进发育中的 OB 中间神经元的形态分化。此外，我们的研究结果表明，BDNF 和 NT-3 可能通过增加突触小结的大小来促进突触成熟。