Low-frequency hippocampal-cortical activity drives brain-wide resting-state functional MRI connectivity

Proc Natl Acad Sci U S A. 2017 Aug 15;114(33):E6972-E6981. doi: 10.1073/pnas.1703309114. Epub 2017 Jul 31.


The hippocampus, including the dorsal dentate gyrus (dDG), and cortex engage in bidirectional communication. We propose that low-frequency activity in hippocampal-cortical pathways contributes to brain-wide resting-state connectivity to integrate sensory information. Using optogenetic stimulation and brain-wide fMRI and resting-state fMRI (rsfMRI), we determined the large-scale effects of spatiotemporal-specific downstream propagation of hippocampal activity. Low-frequency (1 Hz), but not high-frequency (40 Hz), stimulation of dDG excitatory neurons evoked robust cortical and subcortical brain-wide fMRI responses. More importantly, it enhanced interhemispheric rsfMRI connectivity in various cortices and hippocampus. Subsequent local field potential recordings revealed an increase in slow oscillations in dorsal hippocampus and visual cortex, interhemispheric visual cortical connectivity, and hippocampal-cortical connectivity. Meanwhile, pharmacological inactivation of dDG neurons decreased interhemispheric rsfMRI connectivity. Functionally, visually evoked fMRI responses in visual regions also increased during and after low-frequency dDG stimulation. Together, our results indicate that low-frequency activity robustly propagates in the dorsal hippocampal-cortical pathway, drives interhemispheric cortical rsfMRI connectivity, and mediates visual processing.

Keywords: fMRI; hippocampus; low frequency; optogenetic; resting-state functional connectivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebral Cortex* / diagnostic imaging
  • Cerebral Cortex* / physiology
  • Connectome*
  • Dentate Gyrus* / diagnostic imaging
  • Dentate Gyrus* / physiology
  • Magnetic Resonance Imaging*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Rest / physiology*