Opposing intrinsic and synaptic plasticity mechanisms stabilize altered cortical networks during sleep deprivation

Abstract

Sleep deprivation alters brain activity and impairs performance, yet many aspects of behaviour are preserved in this state. In the cortex for example, sleep deprivation increases neuronal firing rates and low-frequency oscillatory activity, but cortical circuits continue to process information. Recent work has implicated synaptic inhibition in these changes, with sleep deprivation causing cortical GABAA receptor (GABAAR) signalling to become depolarizing due to changes in chloride gradients that determine the GABAAR reversal potential (EGABAAR). The impact in the intact brain remains unclear, however, as both the degree and effects of EGABAAR changes depend on network activity and intrinsic properties of neurons. To address this, we perform in vivo gramicidin recordings from cortical pyramidal neurons in sleep-deprived mice. We reveal that synaptic EGABAAR is depolarised to values sufficient to support bona fide excitatory GABAAR signalling, through combined network-dependent and cell-autonomous effects. In the face of this depolarizing drive, cortical neurons engage spike threshold adaptation mechanisms that limit their excitability. These opposing effects stabilise activity in simulations of sleep-deprived cortical networks and reproduce the increased firing rates and low-frequency oscillatory activity. This interplay between intrinsic and synaptic mechanisms may help maintain network stability during sleep deprivation, while reducing flexibility for subsequent adaptation.