Meerlo, P. | bioRxiv Science

bioRxiv2021

Sleep deprivation reduces the density of individual spine subtypes in a branch-specific fashion in CA1 neurons

Sleep deprivation has a negative impact on hippocampus-dependent memory, which are thought to depend on cellular plasticity. We previously found that five hours of sleep deprivation robustly decreases dendritic spine density in the CA1 area of the hippocampus in adult male mice. However, recent work by others suggests that sleep deprivation increases the density of certain spine types on specific dendritic branches. Based on these recent findings and our previous work, we conducted a more in-depth analysis of different spine types on branches 1, 2 and 5 of both apical and basal dendrites to assess whether five hours of sleep deprivation may have previously unrecognized spine-type and branch-specific effects. This analysis shows no spine-type specific changes on branch 1 and 2 of apical dendrites after sleep deprivation. In contrast, sleep deprivation decreases the number of mushroom and branched spines on branch 5. Likewise, sleep deprivation reduces thin, mushroom, and filopodia spine density on branch 5 of the basal dendrites, without affecting spines on branch 1 and 2. Our findings indicate that sleep deprivation leads to local branch-specific reduction in the density of individual spine types, and that local effects might not reflect the overall impact of sleep deprivation on CA1 structural plasticity. Moreover, our analysis underscores that focusing on a subset of dendritic branches may lead to potential misinterpretation of the overall impact of in this case sleep deprivation on structural plasticity.

neuroscience↗

bioRxiv2021

Restoring persistent accessibility to memories after sleep deprivation-induced amnesia

It is well established that sleep deprivation after learning impairs hippocampal memory processes and causes amnesia. It is unknown, however, whether it leads to the actual loss of information or merely suppresses the retrievability of this information stored under suboptimal conditions. Here, we reveal that hippocampal memories formed under sleep deprivation conditions can be successfully retrieved multiple days following training using optogenetic memory engram activation or treatment with the clinically-approved phosphodiesterase 4 (PDE4) inhibitor roflumilast. Moreover, when optogenetic memory engram activation and roflumilast treatment were combined two days following training and subsequent sleep deprivation, it resulted in a more persistent memory trace that allowed for natural (i.e., manipulation free) retrieval several days later. Our studies in mice demonstrate that sleep deprivation does not necessarily cause memory loss, but instead leads to the suboptimal storage of information that is difficult to retrieve. We also provide proof of principle that these suboptimally stored memories can be made accessible again far beyond the learning episode and that the clinically-approved PDE4 inhibitor roflumilast may be used to successfully retrieve information thought to be lost.

neuroscience↗