Brief sleep disruption following hippocampus-dependent learning downscales interneuron synapses within lateral entorhinal cortex.

Study objectives: Brief sleep loss alters cognition and the activity and synaptic structures of both principal neurons and interneurons in hippocampus. However, although sleep-dependent coordination of activity between hippocampus and neocortex is essential for memory consolidation, much less is known about how sleep loss affects neocortical input to hippocampus, or excitatory-inhibitory balance within neocortical structures. We aimed to test how the synaptic structures of SST+ interneurons in lateral and medial entorhinal cortex (LEC and MEC), which are the major neocortical input to hippocampus, are affected by brief sleep disruption in the hours following learning. Methods: We used Brainbow 3.0 to label SST+ interneurons in the LEC or MEC of male Results: Dendritic spine density among EC SST+ interneurons was altered in a subregion-specific manner, with dramatic alterations in dendritic spine type distributions and reductions in spine size in LEC, but not MEC, after post-CFC SD. Conclusions: Our data suggest that the synaptic connectivity of SST+ interneurons is significantly reduced in LEC when learning is followed by sleep disruption. This suggests that post-learning sleep loss disrupts hippocampus-dependent memory processing in part through altered excitatory-inhibitory balance in neocortical structures providing input to hippocampus. They also provide more mechanistic insight into sleep's role in coordinating neocortical-hippocampal communication in the context of memory consolidation.