Journal Article

FZJ-2026-03679

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Sleep differentially modulates synaptic vesicle protein 2A and spine density across cortical regions and development

Ma, J.FZJ* ; Braun, A.FZJ* ; Oskamp, A.FZJ* ; Kricsfalussy-Hrabár, L. ; Hermes, N.FZJ* ; Djakkani, S. ; Holz, U.FZJ* ; Jakobs, S.FZJ* ; Klein, S.FZJ* ; Stüsgen, S.FZJ* ; Krapf, P.FZJ* ; Neumaier, B.FZJ* ; Drzezga, A.FZJ* ; Beer, S.FZJ* ; Bauer, A.FZJ* ; Rollenhagen, A.FZJ* ; Kampa, B.FZJ* ; Elmenhorst, D. (Corresponding author)FZJ*

2026
Elsevier St. Louis

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Please use a persistent id in citations: doi:10.1016/j.isci.2026.116676  doi:10.34734/FZJ-2026-03679

Abstract: Sleep is proposed to regulate synaptic strength; yet, the underlying mechanisms remain debated under the synaptic homeostasis hypothesis (SHY). We examined synaptic vesicle glycoprotein 2A (SV2A) and dendritic spine density in mouse brain across conditions of physiological sleep and sleep deprivation. Spine density decreased during sleep and increased following sleep deprivation, consistent with the SHY. In contrast, [18F]SynVesT-1 positron emission tomography (PET) imaging and [3H]UCB-J autoradiography revealed reduced SV2A following sleep deprivation. Layer-specific analyses in somatosensory and visual cortices further supported coordinated regulation between SV2A and dendritic spines. Developmentally, adolescent mice exhibited higher baseline SV2A and spine density than adults, with greater SV2A sensitivity to sleep deprivation, whereas adults were more responsive to physiological sleep. Together, these findings reveal bidirectional regulation of pre- and postsynaptic compartments and highlight developmental differences in sleep-dependent synaptic organization.

Note: This research was supported by internal institutional funds and the project SleepLess, which received funding from BMBF (grant no. 01EW1808), and FWO and FRQS under the frame of ERA-NET Neuron Cofund. The authors would like to thank Nikola Kornadt-Beck for excellent technical assistance. J.M. would like to thank the China Scholarship Council (CSC) for financial support under grant no. 202106240026.

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Contributing Institute(s):

1. Molekulare Organisation des Gehirns (INM-2)
2. Nuklearchemie (INM-5)

Research Program(s):

1. 5253 - Neuroimaging (POF4-525) (POF4-525)

Appears in the scientific report 2026

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