DIVERSE, STATE-DEPENDENT COUPLING BETWEEN HIPPOCAMPUS AND CORTEX

Animals integrate sensory inputs with intrinsic brain activity related to current goals and previous experience. The balance between extrinsic and intrinsic processing is believed to be regulated along a continuum that is reflected in behavioral measures and correlated with distinct states of synchronization in the hippocampus. To investigate hippocampal-cortical coupling in distinct brain states, we combined chronic extracellular recording of hippocampal activity using ultra-flexible tentacle electrodes (UFTEs) with wide-field calcium imaging of the dorsal cortex in transgenic mice (GP5.17/Thy1) expressing GCaMP6f in pyramidal neurons (Layers 2/3 and 5). Recordings from hippocampal single units were stable across months with consistent synchronization to local population activity. However, within individual recording sessions the activity of hippocampal neurons exhibited diverse patterns of correlation to the dorsal cortex, as assessed from the cortical calcium signals. Thus, it appeared dependent on changes in behavioral state, such as movement as well as ongoing, intrinsic variations in brain state, such as arousal as indexed by pupil diameter. The topographical patterns of coupling between the activity of hippocampal neurons and cortex activation were anatomically specific and fluctuated over long time scales (tens of seconds to minutes). We believe that these diverse, dynamic activity patterns reflect shifts in functional connectivity that may serve distinct functional modes of brain-wide coordination and communication. The combined application of ultra-flexible electrodes and wide-field imaging provides a powerful tool to monitor the integration of local population dynamics on fast time scales with large-scale patterns of coordinated activity across many cortical areas brain.