Neuron-specific interleukin-1 receptor accessory protein (AcPb) modulates sleep- and wake-like states in vivo and in vitro

Interleukin-1 beta (IL1) signals via its type I receptor (IL1R)-accessory protein (AcP) complex. In brain, an alternatively spliced isoform of AcP, AcPb, occurs in neurons. AcPb mRNA increases with sleep loss. Mice lacking AcPb, sleep less after sleep deprivation. Mature neuronal/glial cultures have a default sleep-like state. The sleep-like state becomes more wake-like with electrical stimulation as determined from: (a) action potential burstiness (BI for burstiness index), (b) synchronization of electrical potentials (SYN) and (c) slow wave (0.5–3.5 Hz) (SW) power; these parameters also characterize animal sleep. We cultured cortical cells from WT mice and AcPb knockout mice. After 10–12 days, stable spontaneous values of the BI, SYN and SW power emerged from the WT cells. Electrical stimulation reduced the BI, SYN and SW power values during and after (30 min) stimulation; 24 h later, homeostasis was evidenced by a rebound in BI, SYN and SW power values to higher than pre-stimulation baseline values. Cortical cells from AcPb knockout mice behaved differently. The emergence of the spontaneous sleep-like state was delayed and BI, SYN and SW power values were substantially lower. Electrical stimulation of WT cells reduced BI, SYN and SW power values whereas it was without effect on cultured AcPb cells. We conclude that such cultures are useful to define the genetic and molecular conditions necessary for emergence of network properties such as sleep.