Datta Dibyadeep, Arion Dominique, Lewis David A
Department of Neuroscience Department of Psychiatry, Translational Neuroscience Program, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Psychiatry, Translational Neuroscience Program, University of Pittsburgh, Pittsburgh, PA, USA.
Cereb Cortex. 2015 Aug;25(8):2295-305. doi: 10.1093/cercor/bhu040. Epub 2014 Mar 7.
Cortical pyramidal neuron activity is regulated in part through inhibitory inputs mediated by GABAA receptors. The subunit composition of these receptors confers distinct functional properties. Thus, developmental shifts in subunit expression will likely influence the characteristics of pyramidal cell firing and the functional maturation of processes that depend on these neurons. We used laser microdissection and PCR to quantify postnatal developmental changes in the expression of GABAA receptor subunits (α1, α2, α5, β2, γ2, and δ) in layer 3 pyramidal cells of monkey prefrontal cortex, which are critical for working memory. To determine the specificity of these changes, we examined glutamate receptor subunits (AMPA Glur1 and NMDA Grin1) and conducted the same analyses in layer 5 pyramidal cells. Expression of GABAA receptor subunit mRNAs changed substantially, whereas glutamate receptor subunit changes were modest over postnatal development. Some transcripts (e.g., GABAA α1) progressively increased from birth until adulthood, whereas others (e.g., GABAA α2) declined with age. Changes in some transcripts were present in only one layer (e.g., GABAA δ). The development of GABAA receptor subunit expression in primate prefrontal pyramidal neurons is protracted and subunit- and layer-specific. These trajectories might contribute to the molecular basis for the maturation of working memory.
皮质锥体神经元的活动部分是通过由GABAA受体介导的抑制性输入来调节的。这些受体的亚基组成赋予了不同的功能特性。因此,亚基表达的发育变化可能会影响锥体细胞放电的特征以及依赖于这些神经元的过程的功能成熟。我们使用激光显微切割和PCR技术来量化猕猴前额叶皮层第3层锥体细胞中GABAA受体亚基(α1、α2、α5、β2、γ2和δ)表达的出生后发育变化,这些细胞对工作记忆至关重要。为了确定这些变化的特异性,我们检测了谷氨酸受体亚基(AMPA Glur1和NMDA Grin1),并在第5层锥体细胞中进行了相同的分析。GABAA受体亚基mRNA的表达在出生后发育过程中发生了显著变化,而谷氨酸受体亚基的变化则较小。一些转录本(如GABAA α1)从出生到成年逐渐增加,而其他转录本(如GABAA α2)则随年龄下降。一些转录本的变化仅存在于一层中(如GABAA δ)。灵长类前额叶锥体神经元中GABAA受体亚基表达的发育是持久的,且具有亚基和层特异性。这些变化轨迹可能为工作记忆成熟的分子基础做出贡献。