Postnatal development of synaptic structure proteins in pyramidal neuron axon initial segments in monkey prefrontal cortex.

Postnatal development of synaptic structure proteins in pyramidal neuron axon initial segments in monkey prefrontal cortex.
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DOI:
10.1002/cne.22006
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发表时间:
2009-06-01
期刊:
The Journal of comparative neurology
影响因子:
--
通讯作者:
Lewis DA
Lewis DA
中科院分区:
其他
文献类型:
--
作者:
Cruz DA;Lovallo EM;Stockton S;Rasband M;Lewis DA

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在灵长类前额叶皮层(PFC),某些类别的GABA神经元的突触连接的功能成熟是非常复杂的。例如,调节GABA神经传递的突触前和突触后蛋白水平从皮质中间神经元的枝形吊灯类到锥体神经元的轴突起始段(AIS)在猴PFC的围产期和青春期都经历了显著的变化。为了理解与这些发育细化相关的潜在分子机制,我们定量了PFC的相对密度、层状分布、以及从出生到成年年龄的恒河猴PFC中对锚蛋白-G、β IV血影蛋白或桥蛋白(参与调节突触结构和受体定位的三种蛋白质)免疫反应的锥体神经元AIS的长度。在出生后的前六个月,Ankalo-G-和β IV血影蛋白标记的AIS的密度和长度下降,但随后在青春期和成年期保持稳定。相反,桥蛋白标记的AIS的密度在大约15个月大之前是稳定的,然后在青春期显著下降。因此,定义GABA输入锥体神经元AIS在猴PFC的结构特征的分子决定因素经历不同的发展轨迹与不同类型的变化发生在围产期和青春期。与以前的数据相一致,这些研究结果揭示了一个两阶段的发展过程中的GABA能突触稳定性和GABA神经传递的吊灯细胞输入锥体神经元,可能有助于延长成熟的灵长类PFC电路介导的行为。
In the primate prefrontal cortex (PFC), the functional maturation of the synaptic connections of certain classes of GABA neurons is very complex. For example, the levels of both pre- and post-synaptic proteins that regulate GABA neurotransmission from the chandelier class of cortical interneurons to the axon initial segment (AIS) of pyramidal neurons undergo marked changes during both the perinatal period and adolescence in the monkey PFC. In order to understand the potential molecular mechanisms associated with these developmental refinements, we quantified the relative densities, laminar distributions, and lengths of pyramidal neuron AIS immunoreactive for ankyrin-G, ßIV spectrin, or gephyrin, three proteins involved in regulating synapse structure and receptor localization, in the PFC of rhesus monkeys ranging in age from birth through adulthood. Ankyrin-G- and ßIV spectrin-labeled AIS declined in density and length during the first six months postnatal, but then remained stable through adolescence and into adulthood. In contrast, the density of gephyrin-labeled AIS was stable until approximately 15 months of age and then markedly declined during adolescence. Thus, molecular determinants of the structural features that define GABA inputs to pyramidal neuron AIS in monkey PFC undergo distinct developmental trajectories with different types of changes occurring during the perinatal period and adolescence. In concert with previous data, these findings reveal a two-phase developmental process of GABAergic synaptic stability and GABA neurotransmission at chandelier cell inputs to pyramidal neurons that likely contributes to the protracted maturation of behaviors mediated by primate PFC circuitry.
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