Youssoufian M, Walmsley B
Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia.
Eur J Neurosci. 2007 Mar;25(6):1647-52. doi: 10.1111/j.1460-9568.2007.05428.x.
Neurotrophins are a large class of trophic factors located throughout the central nervous system. While the role of neurotrophins in neuronal survival and axon guidance is well known, their secondary role in modulating synaptic transmission and cell firing properties is largely unexplored. In this study we examined the expression of neurotrophins in the mouse medial nucleus of the trapezoid body (MNTB) and investigated the effect of exogenous brain-derived neurotrophic factor (BDNF) application on the firing properties of MNTB principal cells. The expression levels of nerve growth factor, BDNF, neurotrophin-3, neurotrophin-4/5 and major receptor tyrosine kinase B was found to be moderate to high at postnatal day 12, indicating that the neurotrophins may have a role following synaptogenesis. A 2-h exposure to exogenous BDNF (100 ng/mL) had a significant effect on principal cell firing properties and voltage-gated potassium currents. Importantly, preincubation in BDNF increased the incidence of multifiring and rebounding cells, and significantly increased the number of action potentials fired in response to a single depolarizing step. BDNF exposure also significantly decreased underlying voltage-gated potassium currents, including both the low- and high-voltage-activated components. Our data show that the neurotrophins, specifically BDNF, may have a novel role in modulating cell excitability in the auditory brainstem.
神经营养因子是一大类遍布中枢神经系统的营养因子。虽然神经营养因子在神经元存活和轴突导向中的作用已为人熟知,但其在调节突触传递和细胞放电特性方面的次要作用在很大程度上尚未得到探索。在本研究中,我们检测了小鼠梯形体内侧核(MNTB)中神经营养因子的表达,并研究了外源性脑源性神经营养因子(BDNF)的应用对MNTB主细胞放电特性的影响。在出生后第12天,发现神经生长因子、BDNF、神经营养因子-3、神经营养因子-4/5和主要受体酪氨酸激酶B的表达水平为中度至高度,表明神经营养因子可能在突触形成后发挥作用。暴露于外源性BDNF(100 ng/mL)2小时对主细胞放电特性和电压门控钾电流有显著影响。重要的是,在BDNF中预孵育增加了多重放电和反弹细胞的发生率,并显著增加了响应单个去极化步骤所激发的动作电位数量。BDNF暴露还显著降低了基础电压门控钾电流,包括低电压激活和高电压激活成分。我们的数据表明,神经营养因子,特别是BDNF,可能在调节听觉脑干中的细胞兴奋性方面具有新的作用。