Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1
- University of Pennsylvania, United States
- Columbia University, United States
- University of Groningen, Netherlands
- University of Glasgow, United Kingdom
- University of Michigan, United States
- Nencki Institute of Experimental Biology, Poland
- King's College London, United Kingdom
Abstract
Brief periods of sleep loss have long-lasting consequences such as impaired memory consolidation. Structural changes in synaptic connectivity have been proposed as a substrate of memory storage. Here, we examine the impact of brief periods of sleep deprivation on dendritic structure. In mice, we find that five hours of sleep deprivation decreases dendritic spine numbers selectively in hippocampal area CA1 and increased activity of the filamentous actin severing protein cofilin. Recovery sleep normalizes these structural alterations. Suppression of cofilin function prevents spine loss, deficits in hippocampal synaptic plasticity, and impairments in long-term memory caused by sleep deprivation. The elevated cofilin activity is caused by cAMP-degrading phosphodiesterase-4A5 (PDE4A5), which hampers cAMP-PKA-LIMK signaling. Attenuating PDE4A5 function prevents changes in cAMP-PKA-LIMK-cofilin signaling and cognitive deficits associated with sleep deprivation. Our work demonstrates the necessity of an intact cAMP-PDE4-PKA-LIMK-cofilin activation-signaling pathway for sleep deprivation-induced memory disruption and reduction in hippocampal spine density.
Article and author information
Author details
Funding
National Institutes of Health (1RO1MH086415)
- Ted Abel
National Institutes of Health (RO1, AG017628)
- Ted Abel
Netherlands organization for Scientific Research (postdoctoral fellowship 825.07.029)
- Robbert Havekes
University of Pennsylvania (UPENN rsearch foundation grant)
- Robbert Havekes
- Ted Abel
National Institutes of Health (postdoctoral fellowship, 5K12GM081529)
- Jennifer C Tudor
National Institutes of Health (postdoctoral fellowship, T32 NS077413)
- Sarah L Ferri
European Commission (FP7-PEOPLE-2009-RG-Alco_CaMK)
- Kasia Radwańska
NCN grant Harmonia 2013/08/m/NZ3/00861 (Research grant)
- Kasia Radwańska
Medical Research Council (Grant MR/J007412/1)
- George S Baillie
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC protocols 804240, 804407, 802784) of the University of Pennsylvania and Head Necki Institute of Experimental Biology, Warsaw.
Copyright
© 2016, Havekes et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 21,214
- views
-
- 2,191
- downloads
-
- 194
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1
eLife 5:e13424.
https://doi.org/10.7554/eLife.13424
Further reading
-
- Neuroscience
Perceiving emotions from the movements of other biological entities is critical for human survival and interpersonal interactions. Here, we report that emotional information conveyed by point-light biological motion (BM) triggered automatic physiological responses as reflected in pupil size. Specifically, happy BM evoked larger pupil size than neutral and sad BM, while sad BM induced a smaller pupil response than neutral BM. Moreover, this happy over sad pupil dilation effect is negatively correlated with individual autistic traits. Notably, emotional BM with only local motion features retained could also exert modulations on pupils. Compared with intact BM, both happy and sad local BM evoked stronger pupil responses than neutral local BM starting from an earlier time point, with no difference between the happy and sad conditions. These results revealed a fine-grained pupil-related emotional modulation induced by intact BM and a coarse but rapid modulation by local BM, demonstrating multi-level processing of emotions in life motion signals. Taken together, our findings shed new light on BM emotion processing, and highlight the potential of utilizing the emotion-modulated pupil response to facilitate the diagnosis of social cognitive disorders.
-
- Neuroscience
Channelrhodopsins (ChRs) are light-gated ion channels widely used to optically activate or silence selected electrogenic cells, such as individual brain neurons. Here, we describe identifying and characterizing a set of anion-conducting ChRs (ACRs) from diverse taxa and representing various branches of the ChR phylogenetic tree. The Mantoniella squamata ACR (MsACR1) showed high sensitivity to yellow-green light (λmax at 555 nm) and was further engineered for optogenetic applications. A single amino-acid substitution that mimicked red-light-sensitive rhodopsins like Chrimson shifted the photosensitivity 20 nm toward red light and accelerated photocurrent kinetics. Hence, it was named red and accelerated ACR, raACR. Both wild-type and mutant are capable optical silencers at low light intensities in mouse neurons in vitro and in vivo, while raACR offers a higher temporal resolution.
