Multiscale imaging informs translational mouse modeling of neurological disease

Multiscale neurophysiology reveals that simple motor actions are associated with changes in neuronal firing in virtually every brain region studied. Accordingly, the assessment of focal pathology such as stroke or progressive neurodegenerative diseases must also extend widely across brain areas. To derive mechanistic information through imaging, multiple resolution scales and multimodal factors must be included, such as the structure and function of specific neurons and glial cells and the dynamics of specific neurotransmitters. Emerging multiscale methods in preclinical animal studies that span micro- to macroscale examinations fill this gap, allowing a circuit-based understanding of pathophysiological mechanisms. Combined with high-performance computation and open-source data repositories, these emerging multiscale and large field-of-view techniques include live functional ultrasound, multi- and single-photon wide-scale light microscopy, video-based miniscopes, and tissue-penetrating fiber photometry, as well as variants of post-mortem expansion microscopy. We present these technologies and outline use cases and data pipelines to uncover new knowledge within animal models of stroke, Alzheimer's disease, and movement disorders.