Medical Scientist Training Program, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Translational Neuroscience Program, Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Cereb Cortex. 2021 Mar 31;31(5):2345-2363. doi: 10.1093/cercor/bhaa341.
The functional output of a cortical region is shaped by its complement of GABA neuron subtypes. GABA-related transcript expression differs substantially between the primate dorsolateral prefrontal cortex (DLPFC) and primary visual (V1) cortices in gray matter homogenates, but the laminar and cellular bases for these differences are unknown. Quantification of levels of GABA-related transcripts in layers 2 and 4 of monkey DLPFC and V1 revealed three distinct expression patterns: 1) transcripts with higher levels in DLPFC and layer 2 [e.g., somatostatin (SST)]; 2) transcripts with higher levels in V1 and layer 4 [e.g., parvalbumin (PV)], and 3) transcripts with similar levels across layers and regions [e.g., glutamic acid decarboxylase (GAD67)]. At the cellular level, these patterns reflected transcript- and cell type-specific differences: the SST pattern primarily reflected differences in the relative proportions of SST mRNA-positive neurons, the PV pattern primarily reflected differences in PV mRNA expression per neuron, and the GAD67 pattern reflected opposed patterns in the relative proportions of GAD67 mRNA-positive neurons and in GAD67 mRNA expression per neuron. These findings suggest that differences in the complement of GABA neuron subtypes and in gene expression levels per neuron contribute to the specialization of inhibitory neurotransmission across cortical circuits.
皮质区域的功能输出由其 GABA 神经元亚型组成决定。在灰质匀浆中,灵长类动物背外侧前额皮质 (DLPFC) 和初级视觉 (V1) 皮质之间的 GABA 相关转录物表达存在显著差异,但这些差异的分层和细胞基础尚不清楚。在猴子 DLPFC 和 V1 的第 2 层和第 4 层中定量测定 GABA 相关转录物的水平,揭示了三种不同的表达模式:1)在 DLPFC 和第 2 层中水平更高的转录物 [例如,生长抑素 (SST)];2)在 V1 和第 4 层中水平更高的转录物 [例如,巴胺相关蛋白 (PV)],以及 3)在各层和各区域中水平相似的转录物 [例如,谷氨酸脱羧酶 (GAD67)]。在细胞水平上,这些模式反映了转录物和细胞类型特异性差异:SST 模式主要反映了 SST mRNA 阳性神经元相对比例的差异,PV 模式主要反映了每个神经元中 PV mRNA 表达的差异,而 GAD67 模式反映了 GAD67 mRNA 阳性神经元相对比例和每个神经元中 GAD67 mRNA 表达的相反模式。这些发现表明,GABA 神经元亚型组成和每个神经元中基因表达水平的差异有助于皮质回路中抑制性神经传递的专业化。