Low frequency hippocampal-cortical activity contributes to brain-wide connectivity as measured by resting-state fMRI

The hippocampus, including dorsal dentate gyrus (dDG), and cortex engage in bidirectional communication. We propose that low frequency activities in hippocampal-cortical pathway underlie brain-wide resting-state fMRI (rsfMRI) connectivity to mediate distinct cognitive functions and integrate sensory information. Using optogenetics and fMRI, we determined large-scale spatiotemporal specific hippocampal-cortical activity. Low, but not high, frequency optogenetic stimulation of dDG excitatory neurons evoked robust cortical and subcortical responses, and enhanced interhemispheric hippocampal and cortical rsfMRI connectivity. In addition, pharmacological inactivation of dDG decreased rsfMRI connectivity. These findings directly indicate that low frequency activity propagates in hippocampal-cortical pathway and contributes to brain-wide rsfMRI connectivity.