Homer1a drives homeostatic scaling-down of excitatory synapses during sleep
Open accessAbstract
Synapse remodeling during sleep: General activity and information processing while an animal is awake drive synapse strengthening. This is counterbalanced by weakening of synapses during sleep (see the Perspective by Acsády). De Vivo et al. used serial scanning electron microscopy to reconstruct axon-spine interface and spine head volume in the mouse brain. They observed a substantial decrease in interface size after sleep. The largest relative changes occurred among weak synapses, whereas strong ones remained stable. Diering et al. found that synapses undergo changes in synaptic glutamate receptors during the sleep-wake cycle, driven by the immediate early gene Homer1a. In awake animals, Homer1a accumulates in neurons but is excluded from synapses by high levels of noradrenaline. At the onset of sleep, noradrenaline levels decline, allowing Homer1a to move to excitatory synapses and drive synapse weakening. Science , this issue p. 457 , p. 507 ; see also p. 511
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At the morphological level, synaptic downscaling during sleep is not ubiquitous but may spare some select synapses that are particularly large or were involved in prior encoding, resulting in increased connectivity at these synapses.
“At the morphological level, there is evidence that synaptic downscaling during sleep is not ubiquitous but may spare some select synapses that are particularly large or were involved in prior encoding, resulting in increased connectivity at these synapses 163,164,228,231 (Figure 2C).”
From Sleep—A brain-state serving systems memory consolidation (2023) · cites this paper as [228]
The imaging passage (labeled Abstract in our copy; no page given) shows that sleep-related changes were not uniform: some spines gained GluA1, and low-GluA1 spines showed no change in GluA1 or size. But the larger, high-GluA1 spines disproportionately lost GluA1 and shrank. The passage does not establish that synapses involved in prior encoding were spared or that connectivity increased at them. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe findings overall point to a compartmentalized response in regulation of synaptic scaling during sleep, with both synaptic strengthening and weakening occurring within the same cell during SWS and REM sleep, possibly depending on synapse size, AMPA receptor densities, and immediate early gene levels.
“Interestingly, beyond evidencing the co-occurrence of differential synaptic scaling during sleep at global and local levels, the findings overall point to a compartmentalized response in this regulation.”
From Sleep—A brain-state serving systems memory consolidation (2023) · cites this paper as [228]
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Experimental — accuracy not yet measuredSynaptic GluA1 is dephosphorylated at S831 and S845 during scaling-down and also in the forebrain during sleep.
“Synaptic GluA1 is dephosphorylated at S831 and S845 during scaling-down and also in the forebrain during sleep (Diering et al., 2014, Diering et al., 2017), which together with other observations suggests that homeostatic scaling-down occurs across the forebrain during sleep (Diering et al., 2017).”
From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Diering et al., 2017
HOMER1 is an important protein for synaptic plasticity and memory consolidation because it drives homeostatic scaling-down of excitatory synapses during sleep to remodel synapses and consolidate contextual memory.
“Another protein on this list, HOMER1 (i.e., HOMER1a) is an important protein for synaptic plasticity and memory consolidation because it drives homeostatic scaling-down of excitatory synapses during sleep to remodel synapses and consolidate contextual memory40.”
From Large-scale proteomic analysis of human brain identifies proteins associated with cognitive trajectory in advanced age (2019) · cites this paper as [40]
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- Authors
- Diering, G. H., Nirujogi, R. S., Roth, R. H., Worley, P. F., Pandey, A., & Huganir, R. L.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Nirujogi, Raja S.
- Roth, Richard H.
- Huganir, Richard L.
- ORCID
- Venue
- Science
- Published
- 2017-02-03
- Volume
- 355
- Issue
- 6324
- Pages
- 511-515
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC5382711
- OpenAlex
- W2585275288
- Semantic Scholar
- bf1eb1e2a972bedc7f76ffbde2d36bd194357aaa
- Cited by
- 516
- References
- 35
- Citations by year
- 2026: 30 · 2025: 53 · 2024: 60 · 2023: 31 · 2022: 60 · 2021: 65 · 2020: 55 · 2019: 78 · 2018: 41 · 2017: 41 · 2016: 1
- FWCI
- 28.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (P50MH100024, RO1NS036715, S10OD021844)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- Homer1a, sleep, excitatory synapses, metabotropic glutamate receptors, norepinephrine, adenosine, synaptic plasticity, memory consolidation
- MeSH terms
- Homer Scaffolding Proteins, Adenosine, Animals, Cell Count, Cells, Cultured, Cognition, Homeostasis, Learning, Neurons, Norepinephrine, Sleep, Synapses, Wakefulness, Prosencephalon, Rats, Sprague-Dawley, Receptors, Metabotropic Glutamate, Mice, Rats, Receptor, Metabotropic Glutamate 5
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