Altered synapse formation in the adult somatosensory cortex of brain-derived neurotrophic factor heterozygote mice
Altered synapse formation in the adult somatosensory cortex of brain-derived neurotrophic factor heterozygote mice
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DOI：
10.1523/jneurosci.4040-03.2004
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发表时间：
2004-03-10
影响因子：
5.3
通讯作者：
Welker, E
中科院分区：
文献类型：
--
作者：
Genoud, C;Knott, GW;Welker, E
成人须-桶通路中增加的感觉刺激诱导BDNF的表达以及皮质IV层中的突触形成。在这里，我们调查是否BDNF发挥作用的神经元之间的连接的改变，通过分析的BDNF杂合子小鼠的超微结构，其特征在于BDNF的表达水平降低。使用连续切片电子显微镜，我们测量了突触密度，棘形态，和突触囊泡分布，以显示BDNF水平降低的小鼠具有与野生型对照难以区分的桶神经元。然而，在24小时的触须刺激后，在杂合小鼠中没有突触形成的迹象。尽管兴奋性和抑制性突触之间的平衡在对照中被修改，但在杂合子中保持恒定。兴奋性突触中突触囊泡的分布在杂合子和野生型小鼠中是相同的，并且不受刺激范例的影响。然而，在野生型动物中，脊柱体积不受刺激的影响，但在杂合动物中显著增加。这些结果提供的证据表明，在体内，BDNF在成人皮层电路的结构重排中起着重要的作用，作为一个增加的感觉输入的结果。
Increased sensory stimulation in the adult whisker-to-barrel pathway induces the expression of BDNF as well as synapse formation in cortical layer IV. Here, we investigated whether BDNF plays a role in the alterations of connectivity between neurons by analyzing the ultrastructure of the BDNF heterozygote mouse, characterized by a reduced level of BDNF expression. Using serial section electron microscopy, we measured synapse density, spine morphology, and synaptic vesicle distribution to show that mice with a reduced level of BDNF have a barrel neuropil that is indistinguishable from wild-type controls. After 24 hr of whisker stimulation, however, there is no indication of synapse formation in the heterozygous mouse. Whereas the balance between excitatory and inhibitory synapses is modified in the controls, it remains constant in the heterozygotes. The distribution of synaptic vesicles in excitatory synapses is the same in heterozygous and wild-type mice and is not influenced by the stimulation paradigm. Spine volume, however, is unchanged by stimulation in the wild-type animals, but does increase significantly in the heterozygous animal. These results provide evidence that, in vivo, BDNF plays an important role in the structural rearrangement of adult cortical circuitry as a consequence of an increased sensory input.