Abstract
Hippocampal communication with subcortical circuits reorganizes across sleep-wake states, yet the dynamics of such interactions remain incompletely defined. We simultaneously recorded neuronal spiking and local field potentials from the dorsal hippocampus (CA1 and dentate gyrus) and limbic subcortical nuclei (supramammillary nucleus (SuM) and lateral septum (LS)) in freely behaving rats across the sleep-wake cycle. During quiescent states (non-rapid eye movement (nREM) sleep and quiet wakefulness), sharp-wave ripples dominated hippocampal activity and produced fast, top-down excitation, with large population surges locally in CA1 and DG, and more modest but significant activation in LS and SuM, whereas dentate spikes elicited smaller state-invariant responses. Conversely, in the bottom-up direction, epochs of high-discharge SuM activity were associated with distinct state-dependent effects, characterized by a sharp, time-locked suppression of CA1 neuronal firing and a slower activation of DG units, thereby revealing different temporal scales and state dependence across reciprocal pathways. During activated, theta-enriched states (rapid eye movement (REM) sleep and active wakefulness), spike-field coupling revealed circuit-wide theta coordination. In active wakefulness, SuM bursts produced brief inhibition of CA1 spiking while theta oscillations organized a multiregional firing sequence around the theta cycle trough; yet SuM neurons were not significantly phase-locked. In REM sleep, this pattern inverted, with only SuM neurons significantly phase-locking to theta waves, and preferred firing near the theta cycle peak. Together, these findings identify state-dependent, bidirectional coordination between hippocampus and subcortical nuclei, characterized by ripple-locked top-down hippocampal output during quiescent states and SuM-mediated bottom-up modulation that reconfigures under theta during activated states.