Brief sleep disruption alters synaptic structures among hippocampal and neocortical somatostatin-expressing interneurons.

Study Objectives: Brief sleep loss alters cognition and synaptic structures of principal neurons in hippocampus and neocortex. However, while recording and bioinformatic data suggest that inhibitory interneurons are more strongly affected by sleep loss, it is unclear how sleep and sleep deprivation affect interneurons' synapses. Disruption of the SST+ interneuron population seems to be a critical early sign of neuropathology in Alzheimer's dementia, schizophrenia, and bipolar disorder - and the risk of developing all three is increased by habitual sleep loss. We aimed to test how the synaptic structures of SST+ interneurons in various brain regions are affected by brief sleep disruption.

Methods: We used Brainbow 3.0 to label SST+ interneurons in the dorsal hippocampus, prefrontal cortex, and visual cortex of male transgenic mice, then compared synaptic structures in labeled neurons after a 6-h period of sleep, or gentle handling sleep deprivation (SD) starting at lights on.

Results: Dendritic spine density among SST+ interneurons in both hippocampus and neocortex was altered in a subregion-specific manner, with increased overall and thin spine density in CA1, dramatic increases in spine volume and surface area in CA3, and small but significant decreases in spine size in CA1, PFC and V1.

Conclusions: Our suggest that the synaptic connectivity of SST+ interneurons is significantly altered in a brain region-specific manner by a few hours of sleep loss. This suggests a cell type-specific mechanism by which sleep loss disrupts cognition and alters excitatory-inhibitory balance in brain networks.

Significance Statement: Changes to the function of somatostatin-expressing (SST+) interneurons have been implicated in the etiology of psychiatric and neurological disorders in which both cognition and sleep behavior are affected. Here, we measure the effects of very brief experimental sleep deprivation on synaptic structures of SST+ interneurons in hippocampus and neocortex, in brain structures critical for sleep-dependent memory processing. We find that only six hours of sleep deprivation restructures SST+ interneurons' dendritic spines, causing widespread and subregion-specific changes to spine density and spine size. These changes have the potential to dramatically alter excitatory-inhibitory balance across these brain networks, leading to cognitive disruptions commonly associated with sleep loss.