Sleep deprivation following hippocampus-dependent learning downscales synaptic inputs to lateral and medial entorhinal cortex interneurons

STUDY OBJECTIVES: Brief sleep loss alters cognition and the function of the hippocampus, but it is unclear how it affects neocortical input to hippocampus. We tested how synaptic structures of somatostatin-expressing (SST+) interneurons in lateral and medial entorhinal cortex (LEC and MEC), which are the major neocortical inputs to hippocampus, are affected by brief sleep deprivation (SD) in the hours following learning. METHODS: We used Brainbow 3.0 to label LEC or MEC SST+ interneurons in male mice. We compared their synaptic structures after single trial contextual fear conditioning (CFC) followed by either a 6-h period of ad lib sleep, or gentle handling SD. We also immunohistochemically characterized activity-dependent cFos expression in EC SST- neurons and SST+ interneurons after post-CFC sleep or SD. RESULTS: Post-CFC SD caused dramatic alterations in dendritic spine type distributions and reduced spine size in LEC-but not MEC-after post-CFC SD. In contrast, SD significantly reduced overall dendritic spine density in MEC, but not LEC, SST+ interneurons, without corresponding changes in spine type or size. In both EC subregions, SD increased the relative expression of cFos in SST- neurons vs. SST+ interneurons, driven primarily by reduced cFos expression in SST+ interneurons. CONCLUSIONS: Our data suggest that excitatory synaptic input to SST+ interneurons is reduced in EC after SD, with effects that differ quantitatively and qualitatively between LEC and MEC. Our findings suggest that sleep loss disrupts hippocampus-dependent memory processing in part through altered excitatory/inhibitory balance in EC structures providing input to hippocampus.