Brain-derived neurotrophic factor modulates cerebellar plasticity and synaptic ultrastructure
Brain-derived neurotrophic factor modulates cerebellar plasticity and synaptic ultrastructure
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DOI：
10.1523/jneurosci.22-04-01316.2002
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发表时间：
2002-02-15
影响因子：
5.3
通讯作者：
Segal, RA
中科院分区：
文献类型：
--
作者：
Carter, AR;Chen, CF;Segal, RA
神经营养因子是神经元存活和功能的关键调节因子。在这里，我们表明，TrkB，脑源性神经营养因子（BDNF）的受体，位于平行纤维浦肯野细胞（PF/PC）突触的小脑。为了确定TrkB受体激活对突触形成和功能的影响，我们研究了具有BDNF基因靶向缺失的小鼠的平行纤维到浦肯野细胞突触。虽然在BDNF -/-小鼠中浦肯野细胞树突异常，但PF/PC突触仍然能够形成。突变体动物的免疫组织化学分析显示，形成了许多PF/PC突触与适当的突触前和突触后蛋白质的并列。这些突触是功能性的，并且在诱发EPSC的波形、自发迷你EPSC的振幅或对延长的10 Hz刺激串的响应中没有检测到差异。然而，成对脉冲易化，一种短期可塑性的形式，在BDNF -/-小鼠中显著降低。突触前末梢的详细超微结构分析表明，这种突触功能的变化伴随着突变小鼠突触囊泡总数的增加和对接囊泡比例的减少。这些数据表明，脑源性神经营养因子调节的机制，短期突触可塑性和稳态之间的关系，不同的囊泡池内的终端。
Neurotrophins are key regulators of neuronal survival and function. Here we show that TrkB, the receptor for brain-derived neurotrophic factor (BDNF), is located at parallel fiber to Purkinje cell (PF/PC) synapses of the cerebellum. To determine the effects of TrkB receptor activation on synapse formation and function, we examined the parallel fiber to Purkinje cell synapses of mice with a targeted deletion of the BDNF gene. Although Purkinje cell dendrites are abnormal in BDNF -/- mice, PF/PC synapses are still able to form. Immunohistochemical analysis of mutant animals revealed the formation of numerous PF/PC synapses with the appropriate apposition of presynaptic and postsynaptic proteins. These synapses are functional, and no differences were detected in the waveform of evoked EPSCs, the amplitude of spontaneous mini-EPSCs, or the response to prolonged 10 Hz stimulus trains. However, paired-pulse facilitation, a form of short-term plasticity, is significantly decreased in BDNF -/- mice. Detailed ultrastructural analysis of the presynaptic terminals demonstrated that this change in synaptic function is accompanied by an increase in the total number of synaptic vesicles in mutant mice and a decrease in the proportion of vesicles that are docked. These data suggest that BDNF regulates both the mechanisms that underlie short-term synaptic plasticity and the steady-state relationship between different vesicle pools within the terminal.