The Reuniens Nucleus of the Thalamus has an Essential Role in Coordinating Slow Wave Activity between Neocortex and Hippocampus

Abstract Sleep is a period of profound neural synchrony throughout the brain, a phenomenon involved in various physiological functions. The coordination between neocortex and hippocampus, in particular, appears to be critical for episodic memory, and indeed, enhanced synchrony in this circuit is a hallmark of slow-wave sleep. However, it is unclear how this coordination is mediated. To this end, we examined the role of the thalamic nucleus reuniens (RE), a midline body with reciprocal connections to both prefrontal and hippocampal cortices. Using a combination of electrophysiological, optogenetic and chemogenetic techniques in the urethane-anesthetized rat (a model of forebrain sleep activity), we directly assessed the role of the RE in mediating slow oscillatory synchrony. Using unit recording techniques, we confirmed that RE neurons showed slow rhythmic activity patterns during deactivated forebrain states that were coupled to ongoing slow oscillations. Optogenetic activation of RE neurons or their projection fibres in the cingulum bundle caused an evoked potential in HPC that was maximal at the level of stratum lacunosum-moleculare of CA1. A similar but longer-latency response could be evoked by stimulation of the medial prefrontal cortex that was then abolished by chemogenetic inhibition of the RE. Inactivation of the RE also severely reduced the coherence of the slow oscillation across cortical and hippocampal sites, suggesting that its activity is necessary to couple slow wave activity across these regions. These results indicate an essential role of the RE in coordinating neocortico-hippocampal slow oscillatory activity, which may be fundamental for slow-wave sleep-related episodic memory consolidation. Significance Statement Offline re-activation of neural activity patterns occurring during previous waking periods might provide further activity-dependent solidification of the synaptic connections that would allow this neural information to be encoded more permanently. In other words, brain activity during sleep might benefit memory permanence. In this work, we show how two distant memory-related areas in the brain, the medial prefrontal cortex and the hippocampus, might coordinate their activity during slow-wave activity via an interposed thalamic structure, the nucleus reuniens. This circuit has already been suggested to play an important role during online memory processing; here we show its potential relevance to offline memory consolidation via its powerful ability to coordinate two episodic memory structures during slow wave activity.