Abstract

Current rodent connectome projects are revealing brain structural connectivity with unprecedented resolution and completeness. How subregional structural connectivity relates to subregional functional interactions is an emerging research topic. We describe a method for standardized, mesoscopic-level data sampling from autoradiographic coronal sections of the rat brain, and for correlation-based analysis and intuitive display of cortico-cortical functional connectivity (FC) on a flattened cortical map. A graphic user interface “Cx-2D” allows for the display of significant correlations of individual regions-of-interest, as well as graph theoretical metrics across the cortex. Cx-2D was tested on an autoradiographic data set of cerebral blood flow (CBF) of rats that had undergone bilateral striatal lesions, followed by 4 weeks of aerobic exercise training or no exercise. Effects of lesioning and exercise on cortico-cortical FC were examined during a locomotor challenge in this rat model of Parkinsonism. Subregional FC analysis revealed a rich functional reorganization of the brain in response to lesioning and exercise that was not apparent in a standard analysis focused on CBF of isolated brain regions. Lesioned rats showed diminished degree centrality of lateral primary motor cortex, as well as neighboring somatosensory cortex—changes that were substantially reversed in lesioned rats following exercise training. Seed analysis revealed that exercise increased positive correlations in motor and somatosensory cortex, with little effect in non-sensorimotor regions such as visual, auditory, and piriform cortex. The current analysis revealed that exercise partially reinstated sensorimotor FC lost following dopaminergic deafferentation. Cx-2D allows for standardized data sampling from images of brain slices, as well as analysis and display of cortico-cortical FC in the rat cerebral cortex with potential applications in a variety of autoradiographic and histologic studies.

Highlights

  • Rodents are primary animal models for studying the mammalian brain

  • Two methods have been broadly used for functional connectivity (FC) analysis: interregional, cross-correlation analysis of time series data such as blood oxygen-level dependent signals measured with functional magnetic resonance imaging, and inter-regional correlation analysis of cross-sectional data such as regional cerebral blood flow measured with positron emission www.frontiersin.org

  • MATERIALS AND METHODS We previously developed a software for the measurement, analysis and display of regional cerebral blood flow (rCBF) data obtained from autoradiographic coronal brain sections of the rat [13]

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Summary

Introduction

Recent rodent connectome projects have begun to delineate anatomic connectivities of the rat and mouse brain with unprecedented resolution and completeness [1,2,3]. These connectome data clearly reveal rich and complex connectivity architectures at the subregional/mesoscopic level. How subregional structural connectivity relates to subregional functional interaction is an emerging research topic. The importance of subregional-level functional connectivity (FC) analysis is highlighted by recent reports of FC-based functional segregation within brain structures [4,5,6]. Correlation-based FC analysis quantifies the symmetrical statistical association between individual brain regions [7]. Two methods have been broadly used for FC analysis: interregional, cross-correlation analysis of time series data such as blood oxygen-level dependent signals measured with functional magnetic resonance imaging (fMRI), and inter-regional correlation analysis of cross-sectional data such as regional cerebral blood flow (rCBF) measured with positron emission www.frontiersin.org

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