Danzer Steve C, McNamara James O
Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
J Neurosci. 2004 Dec 15;24(50):11346-55. doi: 10.1523/JNEUROSCI.3846-04.2004.
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.
海马齿状颗粒细胞通过其苔藓纤维轴突独特的突触前终末特化直接兴奋并间接抑制CA3锥体细胞。该苔藓纤维通路在中枢神经系统中含有最高浓度的脑源性神经营养因子（BDNF），然而BDNF是否能够调节兴奋性和/或抑制性通路尚不清楚。为了定位BDNF，将绿色荧光蛋白转基因小鼠的共聚焦显微镜与BDNF免疫组织化学相结合。发现大约一半的突触前颗粒细胞-CA3锥体细胞接触点含有BDNF。此外，增强的神经元活动实际上使与CA3锥体细胞接触的BDNF免疫反应性终末的百分比增加了一倍。令我们惊讶的是，在与抑制性神经元接触的苔藓纤维终末中也发现了BDNF。这些研究表明，苔藓纤维BDNF能够调节对CA3锥体细胞的直接兴奋性和间接前馈抑制性输入，并揭示癫痫活动增加了与CA3锥体细胞接触的表达BDNF的颗粒细胞突触前终末的数量。
