Exercise training reinstates cortico-cortical sensorimotor functional connectivity following striatal lesioning: development and application of a subregional-level analytic toolbox for perfusion autoradiographs of the rat brain.
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.
Department of Biomedical Engineering, Viterbi School of Engineering, School of Medicine, University of Southern California, Los Angeles, CA, USA.
Yu-Hao
YH
Peng
Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine, School of Medicine, University of Southern California, Los Angeles, CA, USA.
Ryan
R
Heintz
Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine, School of Medicine, University of Southern California, Los Angeles, CA, USA.
Zhuo
Z
Wang
Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine, School of Medicine, University of Southern California, Los Angeles, CA, USA.
Yumei
Y
Guo
Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine, School of Medicine, University of Southern California, Los Angeles, CA, USA.
Kalisa G
KG
Myers
Research Service, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA ; Physiology Department, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
Oscar U
OU
Scremin
Department of Biomedical Engineering, Viterbi School of Engineering, School of Medicine, University of Southern California, Los Angeles, CA, USA.
Jean-Michel I
JM
Maarek
Department of Biomedical Engineering, Viterbi School of Engineering, School of Medicine, University of Southern California, Los Angeles, CA, USA ; Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine, School of Medicine, University of Southern California, Los Angeles, CA, USA.
Daniel P
DP
Holschneider
Parkinson’s Disease; brain mapping; cerebral cortex; dopamine; exercise; functional connectivity; motor training; software