Diering, G. H. et al. Homer1a drives homeostatic scaling-down of excitatory synapses during sleep. Science 355, 511â515 (2017).
Wang, Z. et al. Quantitative phosphoproteomic analysis of the molecular substrates of sleep need. Nature 558, 435â439 (2018).
Bruning, F. et al. Sleepâwake cycles drive daily dynamics of synaptic phosphorylation. Science 366, eaav3617 (2019).
Ode, K. L. & Ueda, H. R. Phosphorylation hypothesis of sleep. Front. Psychol. 11, 575328 (2020).
Tatsuki, F. et al. Involvement of Ca2+-dependent hyperpolarization in sleep duration in mammals. Neuron 90, 70â85 (2016).
Funato, H. et al. Forward-genetics analysis of sleep in randomly mutagenized mice. Nature 539, 378â383 (2016).
Mikhail, C., Vaucher, A., Jimenez, S. & Tafti, M. ERK signaling pathway regulates sleep duration through activity-induced gene expression during wakefulness. Sci. Signal. 10, eaai9219 (2017).
Hendricks, J. C. et al. A non-circadian role for cAMP signaling and CREB activity in Drosophila rest homeostasis. Nat. Neurosci. 4, 1108â1115 (2001).
Crocker, A., Shahidullah, M., Levitan, I. B. & Sehgal, A. Identification of a neural circuit that underlies the effects of octopamine on sleep:wake behavior. Neuron 65, 670â681 (2010).
Crocker, A. & Sehgal, A. Octopamine regulates sleep in Drosophila through protein kinase A-dependent mechanisms. J. Neurosci. 28, 9377â9385 (2008).
Wu, M. N. et al. The effects of caffeine on sleep in Drosophila require PKA activity, but not the adenosine receptor. J. Neurosci. 29, 11029â11037 (2009).
Joiner, W. J., Crocker, A., White, B. H. & Sehgal, A. Sleep in Drosophila is regulated by adult mushroom bodies. Nature 441, 757â760 (2006).
Hellman, K., Hernandez, P., Park, A. & Abel, T. Genetic evidence for a role for protein kinase A in the maintenance of sleep and thalamocortical oscillations. Sleep 33, 19â28 (2010).
Park, M. et al. Loss of the conserved PKA sites of SIK1 and SIK2 increases sleep need. Sci. Rep. 10, 8676 (2020).
Honda, T. et al. A single phosphorylation site of SIK3 regulates daily sleep amounts and sleep need in mice. Proc. Natl Acad. Sci. USA 115, 10458â10463 (2018).
Tomita, J. et al. Pan-neuronal knockdown of calcineurin reduces sleep in the fruit fly, Drosophila melanogaster. J. Neurosci. 31, 13137â13146 (2011).
Nakai, Y. et al. Calcineurin and its regulator sra/DSCR1 are essential for sleep in Drosophila. J. Neurosci. 31, 12759â12766 (2011).
Sunagawa, G. A. et al. Mammalian reverse genetics without crossing reveals Nr3a as a short-sleeper gene. Cell Rep. 14, 662â677 (2016).
Amieux, P. S. et al. Increased basal cAMP-dependent protein kinase activity inhibits the formation of mesoderm-derived structures in the developing mouse embryo. J. Biol. Chem. 277, 27294â27304 (2002).
Skalhegg, B. S. et al. Mutation of the Cα subunit of PKA leads to growth retardation and sperm dysfunction. Mol. Endocrinol. 16, 630â639 (2002).
Franken, P., Chollet, D. & Tafti, M. The homeostatic regulation of sleep need is under genetic control. J. Neurosci. 21, 2610â2621 (2001).
Manschwetus, J. T. et al. A stapled peptide mimic of the pseudosubstrate inhibitor PKI inhibits protein kinase A. Molecules 24, 1567 (2019).
Tone, D. et al. Distinct phosphorylation states of mammalian CaMKIIβ control the induction and maintenance of sleep. PLoS Biol. 20, e3001813 (2022).
Nathanson, J. L., Yanagawa, Y., Obata, K. & Callaway, E. M. Preferential labeling of inhibitory and excitatory cortical neurons by endogenous tropism of adeno-associated virus and lentivirus vectors. Neuroscience 161, 441â450 (2009).
Scott, J. D., Glaccum, M. B., Fischer, E. H. & Krebs, E. G. Primary-structure requirements for inhibition by the heat-stable inhibitor of the cAMP-dependent protein kinase. Proc. Natl Acad. Sci. USA 83, 1613â1616 (1986).
Willis, B. S., Niswender, C. M., Su, T., Amieux, P. S. & McKnight, G. S. Cell-type specific expression of a dominant negative PKA mutation in mice. PLoS ONE 6, e18772 (2011).
Clegg, C. H., Correll, L. A., Cadd, G. G. & McKnight, G. S. Inhibition of intracellular cAMP-dependent protein kinase using mutant genes of the regulatory type I subunit. J. Biol. Chem. 262, 13111â13119 (1987).
Orellana, S. A. & McKnight, G. S. Mutations in the catalytic subunit of cAMP-dependent protein kinase result in unregulated biological activity. Proc. Natl Acad. Sci. USA 89, 4726â4730 (1992).
Esteban, J. A. et al. PKA phosphorylation of AMPA receptor subunits controls synaptic trafficking underlying plasticity. Nat. Neurosci. 6, 136â143 (2003).
Gross, G. G. et al. Recombinant probes for visualizing endogenous synaptic proteins in living neurons. Neuron 78, 971â985 (2013).
Li, H. et al. In vivo selection of kinase-responsive RNA elements controlling alternative splicing. J. Biol. Chem. 284, 16191â16201 (2009).
Goebbels, S. et al. Genetic targeting of principal neurons in neocortex and hippocampus of NEX-Cre mice. Genesis 44, 611â621 (2006).
Mansuy, I. M. & Shenolikar, S. Protein serine/threonine phosphatases in neuronal plasticity and disorders of learning and memory. Trends Neurosci. 29, 679â686 (2006).
Sents, W. et al. PP2A inactivation mediated by PPP2R4 haploinsufficiency promotes cancer development. Cancer Res. 77, 6825â6837 (2017).
Blake, J. A. et al. Mouse Genome Database (MGD): knowledgebase for mouseâhuman comparative biology. Nucleic Acids Res. 49, D981âD987 (2021).
Allen, P. B., Ouimet, C. C. & Greengard, P. Spinophilin, a novel protein phosphatase 1 binding protein localized to dendritic spines. Proc. Natl Acad. Sci. USA 94, 9956â9961 (1997).
Zhang, J., Zhang, Z., Brew, K. & Lee, E. Y. Mutational analysis of the catalytic subunit of muscle protein phosphatase-1. Biochemistry 35, 6276â6282 (1996).
Berndt, N., Dohadwala, M. & Liu, C. W. Constitutively active protein phosphatase 1α causes Rb-dependent G1 arrest in human cancer cells. Curr. Biol. 7, 375â386 (1997).
Cohen, P. T. Protein phosphatase 1âtargeted in many directions. J. Cell Sci. 115, 241â256 (2002).
Huang, H. B. et al. Characterization of the inhibition of protein phosphatase-1 by DARPP-32 and inhibitor-2. J. Biol. Chem. 274, 7870â7878 (1999).
Eto, M., Karginov, A. & Brautigan, D. L. A novel phosphoprotein inhibitor of protein type-1 phosphatase holoenzymes. Biochemistry 38, 16952â16957 (1999).
Wang, G. et al. Somatic genetics analysis of sleep in adult mice. J. Neurosci. 42, 5617â5640 (2022).
OâKeefe, S. J., Tamura, J., Kincaid, R. L., Tocci, M. J. & OâNeill, E. A. FK-506- and CsA-sensitive activation of the interleukin-2 promoter by calcineurin. Nature 357, 692â694 (1992).
Shibasaki, F., Price, E. R., Milan, D. & McKeon, F. Role of kinases and the phosphatase calcineurin in the nuclear shuttling of transcription factor NF-AT4. Nature 382, 370â373 (1996).
Miyakawa, T. et al. Conditional calcineurin knockout mice exhibit multiple abnormal behaviors related to schizophrenia. Proc. Natl Acad. Sci. USA 100, 8987â8992 (2003).
Saper, C. B. & Fuller, P. M. Wakeâsleep circuitry: an overview. Curr. Opin. Neurobiol. 44, 186â192 (2017).
Diekelmann, S. & Born, J. The memory function of sleep. Nat. Rev. Neurosci. 11, 114â126 (2010).
Foley, K., McKee, C., Nairn, A. C. & Xia, H. Regulation of synaptic transmission and plasticity by protein phosphatase 1. J. Neurosci. 41, 3040â3050 (2021).
Cho, J. et al. Fear memory consolidation in sleep requires protein kinase A. Learn. Mem. 25, 241â246 (2018).
Thiel, G., Greengard, P. & Sudhof, T. C. Characterization of tissue-specific transcription by the human synapsin I gene promoter. Proc. Natl Acad. Sci. USA 88, 3431â3435 (1991).
Villa, K. L. et al. Inhibitory synapses are repeatedly assembled and removed at persistent sites in vivo. Neuron 89, 756â769 (2016).
Nishiyama, J., Mikuni, T. & Yasuda, R. Virus-mediated genome editing via homology-directed repair in mitotic and postmitotic cells in mammalian brain. Neuron 96, 755â768.e5 (2017).
Niwa, Y. et al. Muscarinic acetylcholine receptors Chrm1 and Chrm3 are essential for REM sleep. Cell Rep. 24, 2231â2247.e7 (2018).
Yoshida, K. et al. Leak potassium channels regulate sleep duration. Proc. Natl Acad. Sci. USA 115, E9459âE9468 (2018).
Naito, Y., Hino, K., Bono, H. & Ui-Tei, K. CRISPRdirect: software for designing CRISPR/Cas guide RNA with reduced off-target sites. Bioinformatics 31, 1120â1123 (2015).
Cho, S. W., Kim, S., Kim, J. M. & Kim, J. S. Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease. Nat. Biotechnol. 31, 230â232 (2013).
Sumiyama, K., Kawakami, K. & Yagita, K. A simple and highly efficient transgenesis method in mice with the Tol2 transposon system and cytoplasmic microinjection. Genomics 95, 306â311 (2010).
Tsujino, K. et al. Establishment of TSH β real-time monitoring system in mammalian photoperiodism. Genes Cells 18, 575â588 (2013).
Challis, R. C. et al. Systemic AAV vectors for widespread and targeted gene delivery in rodents. Nat. Protoc. 14, 379â414 (2019).
Chan, K. Y. et al. Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems. Nat. Neurosci. 20, 1172â1179 (2017).
Yamada, R. G., Matsuzawa, K., Ode, K. L. & Ueda, H. R. An automated sleep staging tool based on simple statistical features of mice electroencephalography (EEG) and electromyography (EMG) data. Eur. J. Neurosci. 60, 5467â5486 (2024).
Virtanen, P. et al. SciPy 1.0: fundamental algorithms for scientific computing in Python. Nat. Methods 17, 261â272 (2020).
Ukai, H., Kiyonari, H. & Ueda, H. R. Production of knock-in mice in a single generation from embryonic stem cells. Nat. Protoc. 12, 2513â2530 (2017).
Ode, K. L. et al. Knockoutârescue embryonic stem cell-derived mouse reveals circadian-period control by quality and quantity of CRY1. Mol. Cell 65, 176â190 (2017).
Kiyonari, H., Kaneko, M., Abe, S. & Aizawa, S. Three inhibitors of FGF receptor, ERK, and GSK3 establishes germline-competent embryonic stem cells of C57BL/6N mouse strain with high efficiency and stability. Genesis 48, 317â327 (2010).
Sato, H., Amagai, K., Shimizukawa, R. & Tamai, Y. Stable generation of serum- and feeder-free embryonic stem cell-derived mice with full germline-competency by using a GSK3 specific inhibitor. Genesis 47, 414â422 (2009).