Analyzing brain connectivity using a genetic reporter for MRI

Motivation: Anatomical connectivity underlies brain function, but currently cannot be traced robustly in living animals. Goal(s): We sought to understand how the structure and plasticity of neuronal projections contribute to functional relationships. Approach: A genetic reporter for MRI was delivered using viral injections and visualization of the reporter was compared with histology, diffusion tractography, and resting state fMRI results. Results: We validated the new tracing tool in mice, showed that some but not all projection strengths correlate with functional measures, and demonstrated that connection strength changes relate variably to functional connectivity changes in a longitudinal model of opioid exposure. Impact: This work validates and applies a genetic reporter for fMRI that permits neuronal projections from viral injection sites to be visualized longitudinally with fidelity in individual animals. Our results help explain functional connectivity relationships in terms of circuit-level contributions.