The mechanisms that underlie the homeostatic drive to sleep remain unclear. Sawada et al. now show that sleep pressure in mice is governed by the synaptic strength of prefrontal cortex (PFC) neurons.

Cortical synapse strength is potentiated during wakefulness and weakened during sleep. The authors of the new work designed a theoretical model of a neuronal network, which predicted that increased excitatory synapse strength would induce coordinated oscillations between ‘up’ (depolarized) and ‘down’ (hyperpolarized) states across neuronal populations, resulting in the slow ‘delta’ waves of synchronous activity that are associated with sleep pressure. Multielectrode array recordings from cultured cortical neurons confirmed that pharmacologically enhancing synapse strength increases delta wave power.