Differential responses of hippocampal subfields to cortical up–down states

The connectivity of the hippocampal trisynaptic circuit, formed by the dentate gyrus, the CA3 and the CA1 region, is well characterized anatomically and functionally in vitro. The functional connectivity of this circuit in vivo remains to be understood. Toward this goal, we investigated the influence of the spontaneous, synchronized oscillations in the neocortical local field potential, reflecting up–down states (UDS) of cortical neurons, on the hippocampus. We simultaneously measured the extracellular local field potential in association cortex and the membrane potential of identified hippocampal excitatory neurons in anesthetized mice. Dentate gyrus granule cells showed clear UDS modulation that was phase locked to cortical UDS with a short delay. In contrast, CA3 pyramidal neurons showed mixed UDS modulation, such that some cells were depolarized during the cortical up state and others were hyperpolarized. CA1 pyramidal neurons, located farther downstream, showed consistent UDS modulation, such that when the cortical and dentate gyrus neurons were depolarized, the CA1 pyramidal cells were hyperpolarized. These results demonstrate the differential functional connectivity between neocortex and hippocampal subfields during UDS oscillations.