Hippocampus-cortex communication during sleep

Abstract

Sleep is critically involved in the formation of long-term memory and is thought to rely on a dialogue between hippocampus and neocortex. The communication between these structures has been proposed to be from the hippocampus to the neocortex. In rodents in the course of sleep, the brain alternates between stages of slow-wave sleep (SWS) and rapid eye movement (REM) sleep. Although sleep stages have been widely investigated, the precise temporal dynamic in hippocampus and cortex has remained largely unresolved. The sleep stages dynamic in hippocampus and cortex might determine the direction of the communication in both areas. Moreover, the hippocampus-cortex communication can be investigated not only in the dynamic of sleep stages, but also restricted to SWS. The interaction between hippocampus and cortex during SWS has been proposed to be top-down regulated by the neocortical slow oscillation (SO) that drives spindles in thalamo-cortical networks and ripples in hippocampal networks. Hippocampal ripples nested in spindles might support the hippocampal-to-neocortical communication. Despite that, these oscillations have been functionally coupled, the temporal association in hippocampus and cortex is not well understood. Furthermore, the thalamus is a central hub that is intimately connected to hippocampus. The thalamus is thought to play an important role in the communication between hippocampus and cortex. However, how thalamic neurons interact with hippocampus is still not clear. Here, we characterized in rats the sleep stages dynamic between neocortex and hippocampus. In addition, we examined the temporal relationships between the specific oscillations during SWS. Lastly, we examined the temporal relationship between thalamic neurons and hippocampal ripples. We simultaneously recorded the electroencephalogram (EEG) from skull electrodes over frontal and parietal cortex and the local field potential (LFP) from the medial prefrontal cortex and dorsal hippocampus (dHC) in order to determine the sleep stage dynamic and the temporal relationship between SOs, spindles and ripples. In addition, we performed simultaneous recordings of thalamic neurons and hippocampal ripples. Our results showed that SWS appeared simultaneously in the hippocampus and the cortex, however REM sleep appeared earlier in the hippocampus. Analysis of the specific oscillations during SWS showed that spindles in the hippocampus are orchestrated by SOs and these spindles modulated hippocampal ripples. Moreover, hippocampal ripples inhibited specifically one class of thalamic neurons. These findings indicated a specific hippocampal-cortex communication, which has clear implications not only for our understanding of the organization of sleep and sleep rhythms, but possibly also for its functions, e.g., in memory formation.