Mapping Optogenetically Driven Single-Vessel fMRI with Concurrent Neuronal Calcium Recordings in the Rat Hippocampus

Extensive in vivo imaging studies investigate the hippocampal neural network function, mainly focusing on the dorsal CA1 region given its optical accessibility. Multi-modality fMRI with simultaneous hippocampal electrophysiological recording reveal broad cortical correlation patterns, but the detailed spatial hippocampal functional map remains lacking given the limited fMRI resolution. In particular, hemodynamic responses linked to specific neural activity are unclear at the single-vessel level across hippocampal vasculature, which hinders the deciphering of the hippocampal malfunction in animal models and the translation to critical neurovascular coupling (NVC) patterns for human fMRI. We simultaneously acquired optogenetically-driven neuronal Ca2+ signals with single-vessel blood-oxygen-level-dependent (BOLD) and cerebral-blood-volume (CBV)-fMRI from individual venules and arterioles. Distinct spatiotemporal patterns of hippocampal hemodynamic responses were correlated to optogenetically evoked and spreading depression-like calcium events. The calcium event-related single-vessel hemodynamic modeling revealed significantly reduced NVC efficiency upon spreading depression-like (SDL) events, providing a direct measure of the NVC function at various hippocampal states. Detailed characterization of large-scale hemodynamic responses linked to specific neural activity remains to be elucidated at the single-vessel level across the subcentimeter scale hippocampal vasculature in vivo. Here, authors use a novel multi-modal fMRI platform to characterize distinct spatiotemporal patterns of hippocampal hemodynamic responses that were correlated to the optogenetically evoked Ca2+ events and to further demonstrate the significantly reduced neurovascular coupling efficiency upon spreading depression-like Ca2+ events.