Sleep Loss Drives Brain Region-Specific and Cell Type-Specific Alterations in Ribosome-Associated Transcripts Involved in Synaptic Plasticity and Cellular Timekeeping

Sleep and sleep loss are thought to impact synaptic plasticity, and recent studies have shown that sleep and sleep deprivation (SD) differentially affect gene transcription and protein translation in the mammalian forebrain. However, much less is known regarding how sleep and SD affect these processes in different microcircuit elements within the hippocampus and neocortex, for example, in inhibitory versus excitatory neurons. Here, we use translating ribosome affinity purification (TRAP) and in situ hybridization to characterize the effects of sleep versus SD on abundance of ribosome-associated transcripts in Camk2a-expressing (Camk2a(+)) pyramidal neurons and parvalbumin-expressing (PV+) interneurons in the hippocampus and neocortex of male mice. We find that while both Camk2a(+) neurons and PV+ interneurons in neocortex show concurrent SD-driven increases in ribosome-associated transcripts for activity-regulated effectors of plasticity and transcriptional regulation, these transcripts are minimally affected by SD in hippocampus. Similarly, we find that while SD alters several ribosome-associated transcripts involved in cellular timekeeping in neocortical Camk2a(+) and PV+ neurons, effects on circadian clock transcripts in hippocampus are minimal, and restricted to Camk2a(+) neurons. Taken together, our results indicate that SD effects on transcripts associated with translating ribosomes are both cell type-specific and brain region-specific, and that these effects are substantially more pronounced in the neocortex than the hippocampus. We conclude that SD-driven alterations in the strength of synapses, excitatory-inhibitory (E-I) balance, and cellular timekeeping are likely more heterogeneous than previously appreciated.

Automated summary

Sleep and sleep deprivation have differential effects on gene transcription and protein translation in the mammalian forebrain, with stronger impacts observed in the neocortex compared to the hippocampus. These effects are cell type-specific and brain region-specific, indicating heterogeneous alterations in synapse strength, excitatory-inhibitory balance, and cellular timekeeping.