Sleep in a dish: key electrophysiological, molecular, and metabolic signatures of sleep and wakefulness revealed in primary cortical cultures

ABSTRACT: Although at the organismal level sleep is defined as a behavioral state, at the level of the cerebral cortex sleep has a distinct local and use-dependent aspect. This observation raises the question whether sleep is a functional property of a complex brain or occurs at the level of neuronal assemblies with populations that were active more during wakefulness needing more intense sleep to recover. Here we show that primary cortical cultures have the capacity to change between sleep- and wake-like states that share key signatures with their in vivo counterparts. Cortical cultures initially exhibit random firing activity that is gradually replaced by a “sleep-like” synchronized burst-pause firing activity as neurons mature and make connections. When stimulated with excitatory neurotransmitters, transient tonic firing is observed, followed by the reappearance of a “sleep-like” state. Besides electrophysiological similarities also the transcriptional profile of stimulated cortical cultures greatly resembles that of the cortex of sleep deprived animals. We then used our in vitro model to map the metabolic pathways activated by the “wake-like” state and found evidence for increased lysolipid release, strongly suggesting that sleep plays a role in neuronal membrane homeostasis. With our in vitro model the cellular and molecular consequences of sleep loss and the genetic determinants of disturbed sleep can now be investigated in a dish. Keywords: stress response

ORGANISM(S): Mus musculus

PROVIDER: GSE33491 | GEO | 2012/08/31

SECONDARY ACCESSION(S): PRJNA148741

REPOSITORIES: GEO