Layer 1 NDNF interneurons form distinct subpopulations with opposite activation patterns during sleep in freely behaving mice

ABSTRACT Non-rapid eye movement (NREM) sleep facilitates memory consolidation by transferring information from the hippocampus to the neocortex. Recent evidence suggests that this transfer occurs primarily when hippocampal sharp-wave ripples (SWRs) and thalamocortical spindles are synchronized. In this study, we asked what role cortical layer 1 NDNF-expressing (L1 NDNF) interneurons play during NREM sleep in gating information transfer during SWR-spindle synchronization. Using simultaneous cell-specific calcium imaging and local field potential recordings in freely moving mice, we discovered that L1 NDNF neurons form cell assemblies tuned to specific sleep stages, exhibiting differential responses to spindle synchronization. L1 NDNF neurons mediate slow inhibition through GABA B receptors. Systemic application of a GABA B receptor antagonist increased pyramidal neuron excitability during NREM sleep, enhanced inhibitory responses during SWRs, and disrupted SWR-spindle coupling. Overall, these findings suggest an important contribution of L1 NDNF neuron-mediated slow inhibition to the synchronization of sleep oscillations with potential implications for memory consolidation processes.