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Abstract

Forming reliable memories requires coordinated activity within distributed brain networks. At present, neural mechanisms underlying systems-level consolidation of declarative memory beyond the hippocampal-prefrontal interactions remain largely unexplored. The mediodorsal thalamic nucleus (MD) is reciprocally connected with the medial prefrontal cortex (mPFC) and also receives inputs from parahippocampal regions. The MD may thus modulate functional connectivity between the hippocampus (HPC) and the mPFC at different stages of information processing. Here, we characterized in freely behaving Sprague Dawley male rats the MD neural activity around hippocampal ripples, indicators of memory replay and hippocampal-cortical information transfer. Overall, the MD firing rate was transiently (0.76 ± 0.06 sec) decreased around ripples with the MD activity suppression preceding the ripple onset for 0.41 ± 0.04 sec (range: 0.01 — 0.95 sec). The degree of MD modulation correlated with ripple amplitude, differed across behavioral states, and also depended on the dynamics of hippocampal-cortical population activity. The MD suppression was the strongest and the most consistent during awake ripples. During NREM sleep, the MD firing decreased around spindle-uncoupled ripples, while enhanced around spindle-coupled ripples. Our results suggest a competitive interaction between the thalamo-cortical and hippocampal-cortical networks supporting ‘online’ and ‘offline’ information processing, respectively. We hypothesize that thalamic activity suppression during spindle-uncoupled ripples is favorable for memory replay as it reduces interference from sensory relay. In turn, the thalamic input during hippocampal-cortical communication, as indicated by spindle/ripple coupling, may contribute to selectivity and reliability of information transfer. Both predictions need to be tested in future experiments.