Neurotrophin 3 potentiates glutamatergic responses of IHC afferents in the cochlea in vivo
Neurotrophin 3 potentiates glutamatergic responses of IHC afferents in the cochlea in vivo
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DOI：
10.1046/j.1460-9568.2000.00049.x
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发表时间：
2000-05-01
影响因子：
3.4
通讯作者：
Felix, D
中科院分区：
文献类型：
--
作者：
Oestreicher, E;Knipper, M;Felix, D
神经营养因子传统上被认为是神经元存活和分化所必需的缓慢作用信号。最近对神经元切片、培养和神经末梢制剂的研究表明，神经营养物质会引起神经活动的急性变化。次级感觉细胞包括内毛细胞（IHC）和味蕾，这些细胞表达其支配神经元存活所必需的神经营养因子。如果在这些细胞中，神经营养因子会像在中枢神经系统（CNS）中一样，严重影响传入神经元的神经活动，这可能对相应的感觉传导过程具有重要的功能影响。神经营养因子NT-3已被报道在造血干细胞中表达。我们选择了一种体内应用系统，用于在IHC的亚突触区域提供NT-3的微离子电泳。研究了NT-3对成年豚鼠内耳自发性和诱发性传入耳蜗神经活动的影响。我们观察到NT-3迅速增加了IHC传入的自发和谷氨酸诱发的放电率。此外，n -甲基-d-天冬氨酸（NMDA）和α -氨基-3-羟基-5-甲基异唑-4-丙酸（AMPA）在NT-3存在时特异性增强，这一过程被酪氨酸激酶受体抑制剂K252a选择性阻断。由于我们不仅将NT-3 mRNA定位在ihc中，还将其定位在螺旋神经节中，因此我们提出，与其他感觉系统类似，传入和自分泌神经营养因子的活性可能与耳蜗神经元的存活有关。此外，NT-3在ihc中可能作为信号依赖性、内在神经调节剂和/或神经保护剂起作用。
Neurotrophins have traditionally been regarded as slow-acting signals essential for neuronal survival and differentiation. Recent studies with neuronal slices, cultures and nerve ending preparations have shown that neurotrophins generate acute changes in nerve activity. Among the secondary sensory cells are the inner hair cells (IHC) and taste buds, cells which express the neurotrophic factors necessary for the survival of their innervating neurons. If in these cells neurotrophins acutely affect the nerve activity of their afferent neurons, as in the central nervous system (CNS), this may have important functional implications for the corresponding sensory transduction processes. The neurotrophin NT-3 has been reported to be expressed in IHCs. We chose an in vivo application system for the microiontophoretic supply of NT-3 in the subsynaptic region of the IHC. The effect of NT-3 on spontaneous and evoked afferent cochlear nerve activities in adult guinea pig inner ear was studied. We observed that NT-3 rapidly increases the spontaneous and glutamate-evoked firing rate of IHC afferents. Moreover, firing induced by both N-methyl-d-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) were specifically enhanced during the presence of NT-3, a process which was selectively blocked by the tyrosine kinase receptor inhibitor K252a. Because we localized NT-3 mRNA not only in IHCs but also in the spiral ganglion, we propose that similar to other sensory systems, afferent and autocrine neurotrophin activities may be responsible for survival of cochlear neurons. In addition, NT-3 in IHCs may operate as a signal-dependent, intrinsic neuromodulator and/or neuroprotector.