Adenosine A1 receptor in the medial parabrachial nucleus modulates sleep-wake regulation and homeostatic processes

Dopp J, Ortega A, Davie K, Poovathingal S, Baz ES, Liu S. Single-cell transcriptomics reveals that glial cells integrate homeostatic and circadian processes to drive sleep–wake cycles. Nat Neurosci. 2024;27:359–72. https://doi.org/10.1038/s41593-023-01549-4.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sayson LV, Jeon SJ, Ortiz DM, Lee HJ, Campomayor NB, Kim HJ, et al. Heukharang (Lactuca sativa L.) extracts enhanced the sleep behavior of mice: potential involvement of adenosine A1 and A2A receptors. Sleep Biol Rhythms. 2024;22:385–94. https://doi.org/10.1007/s41105-024-00522-3.

Article  PubMed  PubMed Central  Google Scholar 

Porkka-Heiskanen T, Strecker RE, Thakkar M, Bjørkum AA, Greene RW, McCarley RW. Adenosine in sleep and wakefulness. Ann Med. 1999;31:125–9. https://doi.org/10.3109/07853899908998788.

Article  CAS  PubMed  Google Scholar 

Xu Q, Wang DR, Dong H, Chen L, Lu J, Lazarus M, et al. Medial parabrachial nucleus is essential in controlling wakefulness in rats. Front Neurosci. 2021;15:645877. https://doi.org/10.3389/fnins.2021.645877.

Article  PubMed  PubMed Central  Google Scholar 

Saper CB, Loewy AD. Commentary on: efferent connections of the parabrachial nucleus in the rat. Brain Res. 2016;1645:15–7. https://doi.org/10.1016/j.brainres.2016.01.009.

Article  CAS  PubMed  Google Scholar 

Martelli D, Stanić D, Dutschmann M. The emerging role of the parabrachial complex in the generation of wakefulness drive and its implication for respiratory control. Respir Physiol Neurobiol. 2013;188:318–23. https://doi.org/10.1016/j.resp.2013.06.019.

Article  PubMed  Google Scholar 

Zhu Y, Ma J, Li Y, Gu M, Feng X, Shao Y, et al. Adenosine-dependent arousal induced by astrocytes in a brainstem circuit. Adv Sci. 2024;11:e2407706. https://doi.org/10.1002/advs.202407706.

Article  CAS  Google Scholar 

Arrigoni E, Chamberlin NL, Saper CB, McCarley RW. Adenosine inhibits basal forebrain cholinergic and noncholinergic neurons in vitro. Neuroscience. 2006;140:403–13. https://doi.org/10.1016/j.neuroscience.2006.02.010.

Article  CAS  PubMed  Google Scholar 

Rainnie DG, Grunze HC, McCarley RW, Greene RW. Adenosine inhibition of mesopontine cholinergic neurons: implications for EEG arousal. Science. 1994;263:689–92. https://doi.org/10.1126/science.8303279.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Scammell TE, Arrigoni E, Lipton JO. Neural circuitry of wakefulness and sleep. Neuron. 2017;93:747–65. https://doi.org/10.1016/j.neuron.2017.01.014.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fulwiler CE, Saper CB. Subnuclear organization of the efferent connections of the parabrachial nucleus in the rat. Brain Res Rev. 1984;319:229–59. https://doi.org/10.1016/0165-0173(84)90012-2.

Article  CAS  Google Scholar 

Zhang L, Zhou S, Tan YF, Gan QF, Koon TH, Wang Z, et al. Collateral projections from the lateral parabrachial nucleus to the bed nucleus of the stria terminalis and the central amygdala in mice. Neurosci Lett. 2025;853:138204. https://doi.org/10.1016/j.neulet.2025.138204.

Article  CAS  PubMed  Google Scholar 

Fuller PM, Sherman D, Pedersen NP, Saper CB, Lu J. Reassessment of the structural basis of the ascending arousal system. J Comp Neurol. 2011;519:933–56. https://doi.org/10.1002/cne.22559.

Article  PubMed  PubMed Central  Google Scholar 

Blanco-Centurion C, Gerashchenko D, Shiromani PJ. Effects of saporin-induced lesions of three arousal populations on daily levels of sleep and wake. J Neurosci. 2007;27:14041–8. https://doi.org/10.1523/JNEUROSCI.3217-07.2007.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Oishi Y, Xu Q, Wang L, Zhang BJ, Takahashi K, Takata Y, et al. Slow-wave sleep is controlled by a subset of nucleus accumbens core neurons in mice. Nat Commun. 2017;8:734. https://doi.org/10.1038/s41467-017-00781-4.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Szymusiak R, McGinty D. Hypothalamic regulation of sleep and arousal. Ann N Y Acad Sci. 2008;1129:275–86. https://doi.org/10.1196/annals.1417.027.

Article  CAS  PubMed  Google Scholar 

Anaclet C, Lin JS, Vetrivelan R, Krenzer M, Vong L, Fuller PM, Lu J. Identification and characterization of a sleep-active cell group in the rostral medullary brainstem. J Neurosci. 2012;32:17970–6. https://doi.org/10.1523/JNEUROSCI.0620-12.2012.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lazarus M, Chen JF, Huang ZL, Urade Y, Fredholm BB. Adenosine and sleep. Handb Exp Pharmacol. 2019;253:359–81. https://doi.org/10.1007/164_2017_36.

Article  CAS  PubMed  Google Scholar 

Porkka-Heiskanen T, Kalinchuk AV. Adenosine, energy metabolism and sleep homeostasis. Sleep Med Rev. 2011;15:123–35. https://doi.org/10.1016/j.smrv.2010.06.005.

Article  PubMed  Google Scholar 

Borbély AA, Daan S, Wirz-Justice A, Deboer T. The two-process model of sleep regulation: a reappraisal. J Sleep Res. 2016;25:131–43. https://doi.org/10.1111/jsr.12371.

Article  PubMed  Google Scholar 

Saper CB, Fuller PM, Pedersen NP, Lu J, Scammell TE. Sleep state switching. Neuron. 2010;68:1023–42. https://doi.org/10.1016/j.neuron.2010.11.032.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shi H, Tu Y, Li Y, Ma C, Gyabaah AT, Yu C, et al. Caffeine excites medial parabrachial nucleus neurons of mice by blocking adenosine A1 receptor. Brain Res. 2022;1790:147984. https://doi.org/10.1016/j.brainres.2022.147984.

Article  CAS  PubMed  Google Scholar 

Kaur S, Pedersen NP, Yokota S, Hur EE, Fuller PM, Lazarus M, et al. Glutamatergic signaling from the parabrachial nucleus plays a critical role in hypercapnic arousal. J Neurosci. 2013;33:7627–40. https://doi.org/10.1523/JNEUROSCI.0173−13.2013.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Frank MG. Astroglial regulation of sleep homeostasis. Curr Opin Neurobiol. 2013;23:812–8. https://doi.org/10.1016/j.conb.2013.02.009.

Article  CAS  PubMed  Google Scholar 

Sawada T, Iino Y, Yoshida K, Okazaki H, Nomura S, Shimizu C, et al. Prefrontal synaptic regulation of homeostatic sleep pressure revealed through synaptic chemogenetics. Science. 2024;385:1459–65. https://doi.org/10.1126/science.adl3043.

Article  CAS  PubMed  Google Scholar 

Wang L, Gao Z, Chen G, Geng D, Gao D. Low levels of adenosine and GDNF are potential risk factors for Parkinson’s disease with sleep disorders. Brain Sci. 2023;13:200. https://doi.org/10.3390/brainsci13020200.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Arrigoni E, Chee MJ, Fuller PM. To eat or to sleep: that is a lateral hypothalamic question. Neuropharmacology. 2019;154:34–49. https://doi.org/10.1016/j.neuropharm.2018.11.017.

Article  CAS  PubMed  Google Schol

Comments (0)

No login
gif