Localization of brain-derived neurotrophic factor to distinct terminals of mossy fiber axons implies regulation of both excitation and feedforward inhibition of CA3 pyramidal cells
Localization of brain-derived neurotrophic factor to distinct terminals of mossy fiber axons implies regulation of both excitation and feedforward inhibition of CA3 pyramidal cells
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DOI：
10.1523/jneurosci.3846-04.2004
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发表时间：
2004-12-15
影响因子：
5.3
通讯作者：
McNamara, JO
中科院分区：
文献类型：
--
作者：
Danzer, SC;McNamara, JO
海马齿状回颗粒细胞直接兴奋和间接抑制CA 3锥体细胞通过不同的突触前终端专业化的苔藓纤维轴突。这种苔藓纤维途径含有CNS中最高浓度的脑源性神经营养因子（BDNF），但BDNF是否被定位为调节兴奋性和/或抑制性途径尚不清楚。采用共聚焦显微镜结合免疫组化技术对绿色荧光蛋白转基因小鼠脑源性神经营养因子进行定位。发现突触前颗粒细胞-CA 3锥体细胞接触的大约一半含有BDNF。此外，增强的神经元活动几乎增加了一倍的百分比接触CA 3锥体细胞的BDNF免疫反应性终端。令人惊讶的是，BDNF也被发现在苔藓纤维终末接触抑制性神经元。这些研究表明，苔藓纤维BDNF准备调节直接兴奋性和间接前馈抑制输入CA 3锥体细胞，并揭示癫痫发作活动增加池BDNF表达颗粒细胞突触前末梢接触CA 3锥体细胞。
Hippocampal dentate granule cells directly excite and indirectly inhibit CA3 pyramidal cells via distinct presynaptic terminal specializations of their mossy fiber axons. This mossy fiber pathway contains the highest concentration of brain-derived neurotrophic factor (BDNF) in the CNS, yet whether BDNF is positioned to regulate the excitatory and/or inhibitory pathways is unknown. To localize BDNF, confocal microscopy of green fluorescent protein transgenic mice was combined with BDNF immunohistochemistry. Approximately half of presynaptic granule cell-CA3 pyramidal cell contacts were found to contain BDNF. Moreover, enhanced neuronal activity virtually doubled the percentage of BDNF-immunoreactive terminals contacting CA3 pyramidal cells. To our surprise, BDNF was also found in mossy fiber terminals contacting inhibitory neurons. These studies demonstrate that mossy fiber BDNF is poised to regulate both direct excitatory and indirect feedforward inhibitory inputs to CA3 pyramdal cells and reveal that seizure activity increases the pool of BDNF-expressing granule cell presynaptic terminals contacting CA3 pyramidal cells.