Elucidating hemodynamics and neuro-glio-vascular signaling using rodent fMRI

Abstract

Despite extensive functional mapping studies using rodent functional magnetic resonance imaging (fMRI), interpreting the fMRI signals in relation to their neuronal origins remains challenging due to the hemodynamic nature of the response. Ultra high-resolution rodent fMRI, beyond merely enhancing spatial specificity, has revealed vessel-specific hemodynamic responses, highlighting the distinct contributions of intracortical arterioles and venules to fMRI signals. This 'single-vessel' fMRI approach shifts the paradigm of rodent fMRI, enabling its integration with other neuroimaging modalities to investigate neuro-glio-vascular (NGV) signaling underlying a variety of brain dynamics. Here, we review the emerging trend of combining multimodal fMRI with opto/chemogenetic neuromodulation and genetically encoded biosensors for cellular and circuit-specific recording, offering unprecedented opportunities for cross-scale brain dynamic mapping in rodent models.

Keywords: functional MRI; neuroimaging; neuromodulation; neurovascular coupling; optogenetics; vasodynamics.

Figure 1:. Vascular Networks Define Functional Area Borders in the Rodent Brain.

This figure showcases high-resolution fMRI images of rodent brains, emphasizing the intricate vascular networks that delineate boundaries between distinct functional areas. The lower panel illustrates various MRI measurement strategies used to detect individual vessels, with brighter voxels indicating venules and darker voxels representing arterioles [77]. Abbreviation: BOLD – blood-oxygen-level-dependent; CBV – cerebral blood volume; CBF/v – cerebral blood flow/velocity. Figure created in part with BioRender.com. Imaging panels from [77]

Figure 2.. Integration of Advanced Neuroteechniques and fMRI for NGV Network Investigation.

The figure presents an integrative approach utilizing advanced neuro-techniques and fMRI to investigate the intricate NGV networks in the brain. The schematic diagram illustrates the combined application of cutting-edge methodologies such as optogenetics, chemogenetics, and fiber photometry-based genetically encoded biosensor recordings alongside high-resolution fMRI. These techniques collectively enable visualization and comprehensive analysis of neuroglial interactions, vascular dynamics, and their integrated role in brain function and pathology. This multidimensional approach could provide valuable insights into the complex interplay of neurons, glial cells (e.g. astrocytes), smooth muscle cells (SMC) and blood vessels, advancing our understanding of neurovascular coupling and its implications for neurological disorders (modified from the graphic abstract of [60])