Modulations in neural circuit dynamics and microstructures can translate to functional enhancements (e.g., upon plasticity), or, conversely, to severe functional deficits (e.g., upon neurodegeneration). We are interested in identifying and investigating the links between such longitudinal functional modulations, their underlying micro-architectural modifications, and the ensuing behavioral responses in vivo. To this end, we harness ultrahigh field Magnetic Resonance Imaging (MRI) coupled to specificity-endowing modalities such as optogenetics and optical microscopy. These offer the opportunity of eliciting activity in circuits of interest, and concomitantly monitoring the ensuing activity in 3D. We further develop and apply novel methodologies based on nonBOLD mechanisms, which can potentially provide much insight into the nature of the activity, as well as probe rather fast dynamics. Microstructures are unraveled via MR methodologies tailored to probe cellular-scale size distributions (in white matter) as well as highly heterogeneous morphologies (in gray matter). These measurements are performed in vivo using state of the art 9.4T and 16.4T scanners, in both anesthetized and behaving rodents, as well as in animal models of neurodegeneration and plasticity. Our long term goals are to understand the mechanisms by which modifications in the tissue’s microstructure transcend globally and modulate function and behavior, and to explore the potential of these as early disease biomarkers.