Grieco Steven F, Wang Gina, Mahapatra Ananya, Lai Cary, Holmes Todd C, Xu Xiangmin
Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, California.
Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana.
J Comp Neurol. 2020 Feb 15;528(3):419-432. doi: 10.1002/cne.24762. Epub 2019 Sep 18.
Neuregulins (NRGs) are protein ligands that impact neural development and circuit function. NRGs signal through the ErbB receptor tyrosine kinase family. NRG1/ErbB4 signaling in parvalbumin-expressing (PV) inhibitory interneurons is critical for visual cortical plasticity. There are multiple types of NRGs and ErbBs that can potentially contribute to visual cortical plasticity at different developmental stages. Thus, it is important to understand the normal developmental expression profiles of NRGs and ErbBs in specific neuron types in the visual cortex, and to study whether and how their expression changes in PV inhibitory neurons and excitatory neurons track with sensory perturbation. Cell type-specific translating ribosome affinity purification and qPCR was used to compare mRNA expression of nrg1,2,3,4 and erbB1,2,3,4 in PV and excitatory neurons in mouse visual cortex. We show that the expression of nrg1 and nrg3 decreases in PV neurons at the critical period peak, postnatal day 28 (P28) after monocular deprivation and dark rearing, and in the adult cortex (at P104) after 2-week long dark exposure. In contrast, nrg1 expression by excitatory neurons is unchanged at P28 and P104 following sensory deprivation, whereas nrg3 expression by excitatory neurons shows changes depending on the age and the mode of sensory deprivation. ErbB4 expression in PV neurons remains consistently high and does not appear to change in response to sensory deprivation. These data provide new important details of cell type-specific NRG/ErbB expression in the visual cortex and support that NRG1/ErbB4 signaling is implicated in both critical period and adult visual cortical plasticity.
神经调节蛋白(NRGs)是影响神经发育和神经回路功能的蛋白质配体。NRGs通过表皮生长因子受体(ErbB)受体酪氨酸激酶家族进行信号传导。在表达小白蛋白(PV)的抑制性中间神经元中,NRG1/ErbB4信号传导对于视觉皮层可塑性至关重要。有多种类型的NRGs和ErbBs,它们可能在不同发育阶段对视觉皮层可塑性产生影响。因此,了解NRGs和ErbBs在视觉皮层特定神经元类型中的正常发育表达谱,以及研究它们在PV抑制性神经元和兴奋性神经元中的表达是否以及如何随感觉扰动而变化,具有重要意义。我们使用细胞类型特异性翻译核糖体亲和纯化和定量PCR来比较小鼠视觉皮层中PV神经元和兴奋性神经元中nrg1、2、3、4和erbB1、2、3、4的mRNA表达。我们发现,在关键期峰值(出生后第28天,即P28)单眼剥夺和暗饲养后,以及在成年皮层(P104)进行为期2周的暗暴露后,PV神经元中nrg1和nrg3的表达下降。相比之下,在感觉剥夺后,兴奋性神经元中nrg1的表达在P28和P104时保持不变,而兴奋性神经元中nrg3的表达则根据年龄和感觉剥夺模式而变化。PV神经元中ErbB4的表达始终保持较高水平,并且似乎不会因感觉剥夺而改变。这些数据提供了视觉皮层中细胞类型特异性NRG/ErbB表达的新的重要细节,并支持NRG1/ErbB4信号传导与关键期和成年视觉皮层可塑性均有关联。