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.

Many neural mechanisms regulate experience-dependent plasticity in the visual cortex (V1) and new techniques for quantifying large numbers of proteins or genes are transforming how plasticity is studied into the era of big data. With those large data sets comes the challenge of extracting biologically meaningful results about visual plasticity from data-driven analytical methods designed for high-dimensional data. In other areas of neuroscience, high-information content methodologies are revealing more subtle aspects of neural development and individual variations that give rise to a richer picture of brain disorders. We have developed an approach for studying V1 plasticity that takes advantage of the known functions of many synaptic proteins for regulating visual plasticity and using that to rebrand the results of high-dimensional analyses into a plasticity phenotype. Here we provide a primer for analyzing experience-dependent plasticity in V1 using example R code to identify high-dimensional changes in a group of proteins. We describe using PCA to classify high-dimensional plasticity features and use them to construct a plasticity phenotype. In the examples, we show how the plasticity phenotype can be visualized and used to identify neurobiological features in V1 that change during development or after different visual rearing conditions. We include an R package "v1hdexplorer" that aggregates the various coding packages and custom visualization scripts written in R Studio.

A collection of glutamatergic and GABAergic proteins participate in regulating experiencedependent plasticity in the visual cortex (V1). Many studies have characterized changes to those proteins caused by monocular deprivation (MD) during the critical period (CP), but less is known about changes that occur when MD stops. We measured the effects of 3 types of visual experience after MD (n=24, 10 male and 14 female); reverse occlusion (RO), binocular deprivation (BD), or binocular vision, on the expression of synaptic proteins in V1 including glutamatergic and GABAergic receptor subunits. Synapsin expression was increased by RO but not affected by the other treatments. BD shifted the balance between glutamatergic and GABAergic receptor subunits to favor GABAAα1. In contrast, BV shifted expression to favor the glutamatergic mechanisms by increasing NMDAR and decreasing GABAAα1 subunits.None of the conditions returned normal expression levels to all of the proteins, but BV was the closest.