Brain-wide analysis of functional and physical connectivity using molecular MRI

The brain’s function depends intimately on its connectivity. We have recently developed a series of molecular tools that enable structure-function relationships to be studied on a brain-wide scale in rodents and nonhuman primates. Here we will describe how a novel genetically encoded activity reporter enables information flow in neural projections to be monitored by fMRI. Using this reporter, we show how the characteristics of efferent population activity from brain regions differ depending on the projection target. Conversely, we show how regional brain activity can be described specifically in terms of synaptically defined input sources. In further studies, we use a second genetic tool for MRI to show how variations in the physical connectivity of the brain relate to functional connectivity in mice. We find that differences in physical and functional connectivity can be dissociated both over individual subjects and over experience, with positive or negative correlations observed in different contexts. These results indicate how molecular imaging techniques enable mechanistic analyses of input/output and structure-function relationships throughout extended brain networks.