Investigation of laminar-specific neurovascular coupling features and pupillometry recording in a newly established awake fMRI model

Abstract

The neuronal firing patterns across cortical layers have been extensively studied to better depict the information flow through neural network. Furthermore, the hemodynamic features have also been investigated by applying the line-scanning fMRI method on animal models. However, the underlying neural correlation to the laminar-specific fMRI signal has not been specified. Here, we established the multi-modal fMRI platform, i.e., concurrent fMRI and intracellular calcium recordings by implementing a multi-slice or bilateral slice line-scanning fMRI method with fiber-based calcium recording system on rodent models to explore the laminar-specific neurovascular coupling features across the cortical layers. Our results demonstrate the calcium leading earlier events than BOLD signals along the cortical layers under evoked and resting-state conditions. In addition, the bilateral BOLD and calcium signals showed diverse coupling features under different stimulation paradigms. These methods allow us to assess the intrinsic spatiotemporal correlation features of neural responses with the laminar-specific fMRI signals in vivo, providing the feasibility of deciphering the altered patterns of fMRI signal across different cortical layers.

Awake rodent fMRI is becoming a promising noninvasive brain imaging modules in recently years, especially combined with behavior or cognition related tasks. However, the fully ‘awake’ brain state remains challenging to interpret, as different restraint protocols and pre-interval anesthesia were, at least in some studies, applied preceding scanning. Furthermore, the motion artifacts and stress level of the awake animals highly dependent on the restraint system and anesthetic agents. Here, in the current project, we successfully established an awake mouse fMRI with pupillary measurement undergoing an intermittent restraint system without any anesthetics. Under visual stimulus, BOLD responses were found in visual-circuit related (visual cortex, dorsal lateral geniculate nuclei, superior colliculus) brain regions. Furthermore, the real-time pupil recordings provide us the stress and motion levels of animals, which severed as a good indicator for our data quality. Thus, this awake mouse fMRI platform provides the possibility for functional longitude imaging and underpins a higher power for ongoing and future translational studies in fully conscious brains.