A HIPPOCAMPAL-THALAMOCORTICAL NEURAL MASS MODEL REVEALS BIDIRECTIONAL REUNIENS-CA1 CONNECTIONS CONTROL SLEEP OSCILLATION COUPLING

Memory consolidation during sleep depends on coordinated slow waves, spindles, and sharp wave-ripples (SWRs) across hippocampo-thalamocortical networks. The reuniens nucleus, bidirectionally connected to medial prefrontal cortex (mPFC) and hippocampus, may mediate this coupling. We developed a neural mass firing rate model comprising two cortical networks representing mPFC layers, two hippocampal networks (CA1 and CA3), and three thalamic nuclei including the reuniens, mediodorsal nucleus, and thalamic reticular nucleus. Each network contains excitatory and inhibitory neuronal populations. Slow waves and sharp waves are spontaneously generated through adaptation and recurrent excitatory connections, while spindles emerge from the mediodorsal-reticular network. The model reproduced experimentally observed temporal relationships: thalamic slow waves lagged cortical slow waves, while thalamic spindles preceded cortical spindles. Phase-amplitude coupling analysis revealed reuniens spindles occur around the slow wave peak while mPFC spindles occur near the trough, with stronger coupling for reuniens. Membrane potentials aligned to cortical slow wave trough showed coordinated deflections across all networks. SWRs were phase-locked to slow waves, occurring before the active phase peak. SWR-triggered averaging showed reuniens membrane potential increases following SWRs. Importantly, SWR rate peaked before cortical spindle onset, suggesting hippocampal events may trigger thalamocortical spindles. Systematic manipulation of bidirectional reuniens-CA1 connection strengths confirmed their essential role in multiregional coordination: stronger connections enhanced the correlation between reuniens and hippocampal membrane potentials during SWRs and tightened the phase-locking of SWRs to cortical slow waves. These findings demonstrate that hippocampo-thalamic synaptic weights mechanistically determine interregional oscillatory synchrony during NREM sleep, thus providing key insights into sleep-dependent memory consolidation.