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 transgenic mice. We then compared synaptic structures in labeled neurons after single trial contextual fear conditioning (CFC) followed by either a 6-h period of sleep, or gentle handling sleep deprivation (SD), focusing on cortical layers providing input to hippocampus.

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.