Siu Caitlin R, Beshara Simon P, Jones David G, Murphy Kathryn M
McMaster Integrative Neuroscience Discovery and Study Program, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
Pairwise Affinity Inc, Dundas, Ontario L9H 2R9, Canada, and.
J Neurosci. 2017 Jun 21;37(25):6031-6042. doi: 10.1523/JNEUROSCI.2304-16.2017. Epub 2017 May 29.
Traditionally, human primary visual cortex (V1) has been thought to mature within the first few years of life, based on anatomical studies of synapse formation, and establishment of intracortical and intercortical connections. Human vision, however, develops well beyond the first few years. Previously, we found prolonged development of some GABAergic proteins in human V1 (Pinto et al., 2010). Yet as >80% of synapses in V1 are excitatory, it remains unanswered whether the majority of synapses regulating experience-dependent plasticity and receptive field properties develop late, like their inhibitory counterparts. To address this question, we used Western blotting of postmortem tissue from human V1 (12 female, 18 male) covering a range of ages. Then we quantified a set of postsynaptic glutamatergic proteins (PSD-95, GluA2, GluN1, GluN2A, GluN2B), calculated indices for functional pairs that are developmentally regulated (GluA2:GluN1; GluN2A:GluN2B), and determined interindividual variability. We found early loss of GluN1, prolonged development of PSD-95 and GluA2 into late childhood, protracted development of GluN2A until ∼40 years, and dramatic loss of GluN2A in aging. The GluA2:GluN1 index switched at ∼1 year, but the GluN2A:GluN2B index continued to shift until ∼40 year before changing back to GluN2B in aging. We also identified young childhood as a stage of heightened interindividual variability. The changes show that human V1 develops gradually through a series of five orchestrated stages, making it likely that V1 participates in visual development and plasticity across the lifespan. Anatomical structure of human V1 appears to mature early, but vision changes across the lifespan. This discrepancy has fostered two hypotheses: either other aspects of V1 continue changing, or later changes in visual perception depend on extrastriate areas. Previously, we showed that some GABAergic synaptic proteins change across the lifespan, but most synapses in V1 are excitatory leaving unanswered how they change. So we studied expression of glutamatergic proteins in human V1 to determine their development. Here we report prolonged maturation of glutamatergic proteins, with five stages that map onto life-long changes in human visual perception. Thus, the apparent discrepancy between development of structure and function may be explained by life-long synaptic changes in human V1.
传统上，基于对突触形成以及皮质内和皮质间连接建立的解剖学研究，人们认为人类初级视觉皮层（V1）在生命的最初几年内就已成熟。然而，人类视觉的发展远远超过最初的几年。此前，我们发现人类V1中一些γ-氨基丁酸能蛋白的发育时间延长（平托等人，2010年）。然而，由于V1中超过80%的突触是兴奋性的，调节经验依赖性可塑性和感受野特性的大多数突触是否像它们的抑制性对应物一样发育较晚，这一问题仍未得到解答。为了解决这个问题，我们对来自人类V1的死后组织（12名女性，18名男性）进行了蛋白质免疫印迹分析，这些组织涵盖了一系列年龄段。然后我们对一组突触后谷氨酸能蛋白（PSD-95、GluA2、GluN1、GluN2A、GluN2B）进行了定量，计算了发育调节的功能对的指数（GluA2:GluN1；GluN2A:GluN2B），并确定了个体间的变异性。我们发现GluN1在早期减少，PSD-95和GluA2在儿童晚期持续发育，GluN2A一直发育到约40岁，并且在衰老过程中GluN2A急剧减少。GluA2:GluN1指数在约1岁时发生变化，但GluN2A:GluN2B指数持续变化，直到约40岁，然后在衰老过程中变回GluN2B。我们还确定幼儿期是个体间变异性增加的一个阶段。这些变化表明，人类V1通过一系列五个精心编排的阶段逐渐发育，这使得V1有可能在整个生命周期中参与视觉发育和可塑性。人类V1的解剖结构似乎在早期就已成熟，但视觉在整个生命周期中都会发生变化。这种差异引发了两种假设：要么V1的其他方面继续变化，要么视觉感知的后期变化依赖于纹外区域。此前，我们表明一些γ-氨基丁酸能突触蛋白在整个生命周期中都会发生变化，但V1中的大多数突触是兴奋性的，它们如何变化仍未得到解答。因此，我们研究了人类V1中谷氨酸能蛋白的表达，以确定它们的发育情况。在此我们报告谷氨酸能蛋白的成熟时间延长，有五个阶段与人类视觉感知的终身变化相对应。因此，结构和功能发育之间的明显差异可能可以通过人类V1中终身的突触变化来解释。
