A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Wake-active brainstem GABA neurons signal sleep pressure by upregulating AMPA receptors to drive recovery sleep; 
Tekijät: Ba, Wei; Harding, Edward C.; Nollet, Mathieu; Tossell, Kyoko; Li, Li-Li; Wong, Sara; Soto, Berta Anuncibay; Yustos, Raquel; Li, Li; Ostaszewska, Jagoda; Zeilhofer, Hanns Ulrich; Vyssotski, Alexei L.; Courtney, Michael J.; Wisden, William; Franks, Nicholas P.
Kustantaja: Elsevier BV
Julkaisuvuosi: 2026
Lehti: Current Biology
Vuosikerta: 36
Numero: 11
Aloitussivu: 2823
Lopetussivu: 2839.e4
ISSN: 0960-9822
eISSN: 1879-0445
DOI: https://doi.org/10.1016/j.cub.2026.04.059
Julkaisun avoimuus kirjaamishetkellä: Avoimesti saatavilla
Julkaisukanavan avoimuus : Osittain avoin julkaisukanava
Verkko-osoite: https://doi.org/10.1016/j.cub.2026.04.059
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/526473618
Rinnakkaistallenteen lisenssi: CC BY
Rinnakkaistallennetun julkaisun versio: Kustantajan versio
How the brain compensates for sleep deprivation (SD) by generating recovery sleep (RS) is not understood. Using Ca²⁺ photometry, we identified a WAKE/rapid eye movement sleep (REMS)-active somatostatin/parvalbumin GABAergic population in the mouse brainstem oral pontine reticular nucleus (PnOVgat). Following SD, PnOVgat cells transiently switched for the first hour to higher activity during non-REMS (NREMS), promoting RS. Chemogenetic activation of PnOVgat neurons prolonged NREMS, whereas ablation blunted electroencephalogram (EEG) delta power rebound and slowed RS accumulation. During RS, the selective switch of PnOVgat cells to having higher Ca2+ levels in NREMS correlated with elevated levels of synaptic proteins PSD95, activated calmodulin-dependent kinase II CaMKII (pCaMKII T286), activated PKA (pPKA T197), and GluA1-containing AMPA receptor subunits with enhanced serine phosphorylation. All increases started during SD and persisted after the first hour of RS. Patch-clamp recordings demonstrated increased postsynaptic AMPA/sleep homeostasis (NMDA) receptor ratios in PnOVgat cells 1 h after RS, indicating increased excitability and greater capacity to drive RS. In contrast, an intermingled population of GABA/glycinergic neurons did not respond to SD, despite having similar baseline WAKE/REMS activities and an ability to promote NREMS. The PnO also contained an intermingled population of excitatory PnOVglut2 WAKE/REMS-active neurons; lesioning them caused hypoactivity, but sleep or WAKE amounts were unaffected. The synaptic homeostasis hypothesis (SHY) proposes that as wakefulness progresses, synaptic AMPA receptor activity is enhanced, and subsequently downregulated during NREMS to rebalance circuit function. We suggest that a variation of SHY implements catching up on lost sleep, with glutamate receptor plasticity in the PnO tracking time awake and adjusting NREMS amounts accordingly.
Avainsanat:
brainstem, oral pons, Sleep deprivation, sleep homeostasis, sleep rebound, synaptic plasticity
Ladattava julkaisu This is an electronic reprint of the original article. |  |
Julkaisussa olevat rahoitustiedot:
This work was supported by grants from: the Wellcome Trust (220759/Z/20/Z to N.P.F. and W.W.), the UK Dementia Research Institute (UK DRI-5004 to N.P.F. and W.W.), the Medical Research Council (APP9329 to N.P.F., S.W., and W.W.), the Rubicon Research Program of the Netherlands Organization for Scientific Research (NWO) (019.161LW.010 to W.B.), the People Program (Marie Curie Actions) of the European Union’s Eight Framework Program H2020 under REA grant agreement 753548 (to W.B.), the Research Council of Finland (grant nos. 348983 to M.J.C. and 346939 to L.-L.L.) and the Magnus Ehrnrooth Foundation, Finland (to L.-L.L.). The Facility for Imaging by Light Microscopy (FILM) at Imperial College London was in part supported by funding from the Wellcome Trust (grant 104931/Z/14/Z) and BBSRC (grant BB/L015129/1).
