Genetic evidence that brain-derived neurotrophic factor mediates competitive interactions between individual cortical neurons

Genetic evidence that brain-derived neurotrophic factor mediates competitive interactions between individual cortical neurons
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DOI:
10.1073/pnas.1206492109
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发表时间:
2012-11-20
影响因子:
11.1
通讯作者:
Jones, Kevin R.
Jones, Kevin R.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
English, Christopher N.;Vigers, Alison J.;Jones, Kevin R.

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脑源性神经营养因子(BDNF)是一种分泌性蛋白质,对新皮层神经回路的发育和功能起重要作用。虽然已经确定BDNF有助于树突结构的塑造和突触强度的调节,但这些功能背后的BDNF信号传导的范围和方向还不完全清楚。为了深入了解BDNF在单个神经元水平上的作用,我们测试了视皮层2/3层神经元中BDNF的细胞自主要求。我们发现,一个神经元携带的功能性Bdnf等位基因的数量相对于占主导地位的基因型决定了其树突棘的密度,树突棘是大多数兴奋性突触的结构。这种对BDNF的需求存在于出生后发育和成年期,这表明神经元能够产生的BDNF的量决定了它在新皮层环境中持续竞争的成功。我们的研究结果表明,BDNF可能执行一个长期寻求的功能,作为一种分泌的生长因子,在介导的竞争性事件,塑造个别神经元和他们的电路。
Brain-derived neurotrophic factor (BDNF) is a secreted protein important for development and function of neocortical circuitry. Although it is well established that BDNF contributes to the sculpting of dendrite structure and modulation of synapse strength, the range and directionality of BDNF signaling underlying these functions are incompletely understood. To gain insights into the role of BDNF at the level of individual neurons, we tested the cell-autonomous requirements for Bdnf in visual cortical layer 2/3 neurons. We found that the number of functional Bdnf alleles a neuron carries relative to the prevailing genotype determines its density of dendritic spines, the structures at which most excitatory synapses are made. This requirement for Bdnf exists both during postnatal development and in adulthood, suggesting that the amount of BDNF a neuron is capable of producing determines its success in ongoing competition in the environment of the neocortex. Our results suggest that BDNF may perform a long-sought function for a secreted growth factor in mediating the competitive events that shape individual neurons and their circuits.