The tired hippocampus: the molecular impact of sleep deprivation on hippocampal function

Abstract

Memory consolidation, the process by which information is stored following training, consists of synaptic consolidation and systems consolidation. It is widely acknowledged that sleep deprivation has a profound effect on synaptic consolidation, particularly for memories that require the hippocampus. It is unclear, however, which of the many molecular changes associated with sleep deprivation directly contribute to memory deficits. In this review, we highlight recent studies showing that sleep deprivation impairs hippocampal cAMP and mTOR signaling, and ultimately causes spine loss in CA1 neurons in a cofilin-dependent fashion. Reversing these molecular alterations made memory consolidation resistant to the negative impact of sleep deprivation. Together, these studies have started to identify the molecular underpinnings by which sleep deprivation impairs synaptic consolidation.

Figure 1. The molecular impact of sleep deprivation

A schematic overview of hippocampal signaling pathways whose modulation by sleep deprivation may contribute to effects on memory formation. Sleep deprivation has been reported to reduce glutamatergic signaling while increasing adenosine levels. Sleep deprivation also attenuates cAMP signaling, CREB-mediated gene transcription, translational processes through mTOR signaling, and structural plasticity through modulation of the PKA-LIMK-cofilin pathway. 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 blue arrows pointing down indicate attenuation of the signaling pathway. Red lines and upward pointing arrows indicate an increase of the signaling pathway.

Figure 2. Sleep deprivation affects hippocampus-dependent memory consolidation in a specific time window following training

Sleep deprivation has the biggest impact on hippocampal memory consolidation in the first few hours following training when it overlaps with the second wave of cAMP signaling, transcription, and protein synthesis critical for increasing synaptic efficacy and memory storage.