Sequential Changes in AMPA Receptor Targeting in the Developing Neocortical Excitatory Circuit
Sequential Changes in AMPA Receptor Targeting in the Developing Neocortical Excitatory Circuit
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DOI：
10.1523/jneurosci.3229-08.2008
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发表时间：
2008-12-17
影响因子：
5.3
通讯作者：
Huguenard, John R.
中科院分区：
文献类型：
--
作者：
Brill, Julia;Huguenard, John R.
许多主要神经元经历从GluR 2缺乏到GluR 2含有的突触谷氨酸受体的早期发育转换。我们测试了大鼠体感皮层兴奋性神经元中GluR 2开关的一般性和时间。以往的研究表明，这种转换发生在出生后第14天（P14）和P16之间的第5层锥体神经元。我们表明，使用细胞内精胺的敏感性，P12和P14之间发生类似的开关在第2/3层锥体细胞和P7和P8之间在第4层星状细胞。通过证明对1-萘乙酰精胺阻断的敏感性和大的单通道电导，证实了P12前2/3层锥体细胞中存在缺乏GluR 2的受体。GluR 2和突触后蛋白PSD 95在P10、P14和P24大鼠的组织中显示出进行性共定位，反映了电生理学的发展。为了区分GluR 2表达或靶向的变化是否是开关的基础，我们利用笼状谷氨酸的局部光解表征了树突状AMPA受体反应。与突触反应相反，在所有年龄段（P6-P40）研究的树突反应的特征是含GluR 2受体。此外，树突和突触诱发的反应显示相应的减少NMDA/AMPA比率在锥体细胞，这表明平行的机制，调节神经元钙水平。这些数据表明，GluR 2开关的结果从AMPA受体靶向的变化在出生后早期的发展，而不是以下皮层发育的层状序列，它依次从层4层到层2/3，最后到层5 b。
Many principal neurons undergo an early developmental switch from GluR2-lacking to GluR2-containing synaptic glutamate receptors. We tested the generality and timing of the GluR2 switch in excitatory neurons of rat somatosensory cortex. Previous studies show that the switch occurs between postnatal day 14 (P14) and P16 in layer 5 pyramidal neurons. We show, using sensitivity to intracellular spermine, that a similar switch occurs between P12 and P14 in layer 2/3 pyramidal cells and between P7 and P8 in layer 4 stellate cells. The presence of GluR2-lacking receptors in layer 2/3 pyramidal cells before P12 was confirmed by demonstrating sensitivity to blockade by 1-naphthyl-acetyl-spermine and large single-channel conductances. GluR2 and the postsynaptic protein PSD95 show progressive colocalization in tissue from P10, P14, and P24 rats, mirroring electrophysiological developments. To distinguish whether changes in GluR2 expression or targeting underlie the switch, we characterized dendritic AMPA receptor responses using focal photolysis of caged glutamate. Contrary to synaptic responses, dendritic responses at all ages studied (P6-P40) were characteristic of GluR2-containing receptors. In addition, dendritically and synaptically evoked responses showed a corresponding decrease in NMDA/AMPA ratios in pyramidal cells, suggesting parallel mechanisms that regulate neuronal calcium levels. These data suggest that the GluR2 switch results from changes in AMPA receptor targeting during early postnatal development, and that rather than following the laminar sequence of cortical development, it proceeds sequentially from layer 4 to layer 2/3 and finally to layer 5b.