The impact of sleep deprivation on neuronal and glial signaling pathways important for memory and synaptic plasticity

Abstract

Sleep deprivation is a common feature in modern society, and one of the consequences of sleep loss is the impairment of cognitive function. Although it has been widely accepted that sleep deprivation affects learning and memory, only recently has research begun to address which molecular signaling pathways are altered by sleep loss and, more importantly, which pathways can be targeted to reverse the memory impairments resulting from sleep deprivation. In this review, we discuss the different methods used to sleep deprive animals and the effects of different durations of sleep deprivation on learning and memory with an emphasis on hippocampus-dependent memory. We then review the molecular signaling pathways that are sensitive to sleep loss, with a focus on those thought to play a critical role in the memory and synaptic plasticity deficits observed after sleep deprivation. Finally, we highlight several recent attempts to reverse the effects of sleep deprivation on memory and synaptic plasticity. Future research building on these studies promises to contribute to the development of novel strategies to ameliorate the effects of sleep loss on cognition.

Figure 1

A schematic overview of hippocampal signalling pathways whose modulation by sleep deprivation may contribute to the effects of sleep deprivation on memory formation. (A) Signalling pathways under baseline conditions. (B) Sleep deprivation has been reported to reduce glutamatergic signalling and cholinergic signalling while increasing adenosine levels and GABAergic signalling. Sleep deprivation also attenuates cAMP signalling and CREB-mediated gene transcription. All of these molecular events are shown in a single connected pathway in order to demonstrate how the effects of sleep deprivation could potentially interact to impact learning and memory. Dashed black lines and black arrows pointing down indicate attenuation of the signalling pathway. Red lines and upward pointing arrows indicate an increase of the signalling pathway.