Abstract

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. We use that knowledge to rebrand protein measurements into plasticity features and combine those 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 to use this analytical framework to study and compare experience-dependent development and plasticity of V1 and apply the plasticity phenotype to translational research questions. We include an R package “PlasticityPhenotypes” that aggregates the coding packages and custom code written in RStudio to construct and analyze plasticity phenotypes.

Highlights

  • Development of the primary visual cortex (V1) is regulated by many neurobiological mechanisms that form a complex set of cellular and molecular states to enhance or reduce experiencedependent plasticity

  • The data sets used for the examples in this paper come from our studies of V1 development and plasticity in cats (Beston et al, 2010; Balsor et al, 2019b), rats (Beshara et al, 2015) and humans (Murphy et al, 2005; Pinto et al, 2010, 2015; Williams et al, 2010; Siu et al, 2017)

  • The workflow was tested on three different study designs including, small-N cross-sectional development studies, a small-N exploratory study of treatments after monocular deprivation (MD) and a larger-N study examining the effects of fluoxetine on adult rats V1

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Summary

Introduction

Development of the primary visual cortex (V1) is regulated by many neurobiological mechanisms that form a complex set of cellular and molecular states to enhance or reduce experiencedependent plasticity. The complexity of the data is posing new challenges for understanding the molecular mechanisms (proteins or genes) that underpin. Big-data studies of protein or gene expression hold the potential of revealing subtle aspects of V1 development and plasticity that might affect visual function. Those studies can enhance translation from animal models to humans by measuring the same plasticity features in different species. We present a primer for discovering collections of plasticity-related proteins, rebranding those into plasticity features, combining features to construct a plasticity phenotype, and using the phenotype to classify normal and abnormal development of V1

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