A brief period of sleep deprivation causes spine loss in the dentate gyrus of mice

Abstract

Sleep and sleep loss have a profound impact on hippocampal function, leading to memory impairments. Modifications in the strength of synaptic connections directly influences neuronal communication, which is vital for normal brain function, as well as the processing and storage of information. In a recently published study, we found that as little as five hours of sleep deprivation impaired hippocampus-dependent memory consolidation, which was accompanied by a reduction in dendritic spine numbers in hippocampal area CA1. Surprisingly, loss of sleep did not alter the spine density of CA3 neurons. Although sleep deprivation has been reported to affect the function of the dentate gyrus, it is unclear whether a brief period of sleep deprivation impacts spine density in this region. Here, we investigated the impact of a brief period of sleep deprivation on dendritic structure in the dentate gyrus of the dorsal hippocampus. We found that five hours of sleep loss reduces spine density in the dentate gyrus with a prominent effect on branched spines. Interestingly, the inferior blade of the dentate gyrus seems to be more vulnerable in terms of spine loss than the superior blade. This decrease in spine density predominantly in the inferior blade of the dentate gyrus may contribute to the memory deficits observed after sleep loss, as structural reorganization of synaptic networks in this subregion is fundamental for cognitive processes.

Circadian Rhythms of Perineuronal Net Composition

“…We speculate that diurnal molecular modifications of PNNs may contribute to memory formation and consolidation mechanisms during the wake/sleep cycle, favoring activity-driven synaptogenesis and synaptic refinement, respectively. For instance, our results on the effects of 5 hour sleep deprivation on WFA+ PNNs in the mouse hippocampus are consistent with reports that 5 hours of sleep deprivation prevents changes in dendritic spine densities in the hippocampus occurring during sleep (Havekes et al, 2016;Raven et al, 2018;Spano et al, 2019;Gisabella et al, 2020). PNN rhythms observed in our study may reflect ongoing systemic and synaptic consolidation during sleep proposed by Rasch and Born (Rasch and Born, 2013).…”

“…Sleep deprivation by gentle handling has been previously shown to prevent synaptic modification that occurs in the hippocampus during sleep in rodents (Havekes et al, 2016;Raven et al, 2018). Here, we use the same approach to test the hypothesis that sleep deprivation prevents the decrease of WFA+ PNNs in the mouse hippocampus.…”

Phosphodiesterase inhibitors roflumilast and vardenafil prevent sleep deprivation‐induced deficits in spatial pattern separation

“…Decreased levels of hippocampal cAMP negatively impact neuronal connectivity through cAMP‐PKA‐LIMK‐cofilin signaling and attenuating PDE4A5 function prevents these changes including the aforementioned spatial memory deficits (Havekes, Park, Tolentino, et al, ; Havekes, Park, Tudor, et al, ). Similar changes in neuronal connectivity have been observed in the DG after SD (Raven et al, ). In future studies, it will, therefore, be interesting to examine whether the impairments in the OPS are a direct result of increased PDE4A5 function specifically in the DG.…”

“…The latter becomes even more interesting as neuronal connectivity in the DG itself is disrupted by sleep loss (Meerlo, Mistlberger, Jacobs, Heller, & McGinty, ; Raven, Meerlo, Van der Zee, Abel, & Havekes, ). Moreover, sleep loss is a common feature of the aforementioned disorders characterized by deficits in pattern separation (e.g., Kheirbek, Klemenhagen, Sahay, & Hen, ; Van Erum, Van Dam, & De Deyn, ; van Goethem, van Hagen, & Prickaerts, ; van Os & Kapur, ).…”

The p75 Neurotrophin Receptor Is an Essential Mediator of Impairments in Hippocampal-Dependent Associative Plasticity and Memory Induced by Sleep Deprivation

“…Error bars indicate ϮSEM. count for these region-specific changes remain to be investigated (Havekes et al, 2016b;Raven et al, 2019). Thus, we postulated that the RhoA-ROCK2 and cAMP-PKA-LIMK1-cofilin pathways in the CA1 and dentate gyrus regions may be more vulnerable to the negative consequences of SD.…”