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 the hippocampus and neocortex. However, while in vivo recording and bioinformatic data suggest that inhibitory interneurons are more strongly affected by sleep loss, it is unclear how sleep and sleep deprivation (SD) affect interneurons' synapses. Disruption of the somatostatin-expressing (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 SST-CRE transgenic mice, then compared synaptic structures in labeled neurons after a 6-hour period of ad lib sleep, or gentle handling 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 changes (primarily decreases) in spine size in CA1, PFC, and V1.

Conclusions: We 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.