{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T18:55:09Z","timestamp":1775156109808,"version":"3.50.1"},"reference-count":51,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T00:00:00Z","timestamp":1680652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004564","name":"the Ministry of Science, Technological Development and Innovation of the Republic of Serbia","doi-asserted-by":"publisher","award":["451-03-47\/2023-01\/200007"],"award-info":[{"award-number":["451-03-47\/2023-01\/200007"]}],"id":[{"id":"10.13039\/501100004564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We traced the changes in GABAergic parvalbumin (PV)-expressing interneurons of the hippocampus and reticulo-thalamic nucleus (RT) as possible underlying mechanisms of the different local cortical and hippocampal electroencephalographic (EEG) microstructures during the non-rapid-eye movement (NREM) sleep compared with anesthesia-induced unconsciousness by two anesthetics with different main mechanisms of action (ketamine\/diazepam versus propofol). After 3 h of recording their sleep, the rats were divided into two experimental groups: one half received ketamine\/diazepam anesthesia and the other half received propofol anesthesia. We simultaneously recorded the EEG of the motor cortex and hippocampus during sleep and during 1 h of surgical anesthesia. We performed immunohistochemistry and analyzed the PV and postsynaptic density protein 95 (PSD-95) expression. PV suppression in the hippocampus and at RT underlies the global theta amplitude attenuation and hippocampal gamma augmentation that is a unique feature of ketamine-induced versus propofol-induced unconsciousness and NREM sleep. While PV suppression resulted in an increase in hippocampal PSD-95 expression, there was no imbalance between inhibition and excitation during ketamine\/diazepam anesthesia compared with propofol anesthesia in RT. This increased excitation could be a consequence of a lower GABA interneuronal activity and an additional mechanism underlying the unique local EEG microstructure in the hippocampus during ketamine\/diazepam anesthesia.<\/jats:p>","DOI":"10.3390\/ijms24076769","type":"journal-article","created":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T02:59:43Z","timestamp":1680663583000},"page":"6769","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Different Alterations of Hippocampal and Reticulo-Thalamic GABAergic Parvalbumin-Expressing Interneurons Underlie Different States of Unconsciousness"],"prefix":"10.3390","volume":"24","author":[{"given":"Ljiljana","family":"Radovanovic","sequence":"first","affiliation":[{"name":"Institute of Biological Research \u201cSinisa Stankovic\u201d, National Institute of the Republic of Serbia, University of Belgrade, 11060 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Novakovic","sequence":"additional","affiliation":[{"name":"Institute of Biological Research \u201cSinisa Stankovic\u201d, National Institute of the Republic of Serbia, University of Belgrade, 11060 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jelena","family":"Petrovic","sequence":"additional","affiliation":[{"name":"Institute of Biological Research \u201cSinisa Stankovic\u201d, National Institute of the Republic of Serbia, University of Belgrade, 11060 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6903-9056","authenticated-orcid":false,"given":"Jasna","family":"Saponjic","sequence":"additional","affiliation":[{"name":"Institute of Biological Research \u201cSinisa Stankovic\u201d, National Institute of the Republic of Serbia, University of Belgrade, 11060 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1038\/nn913","article-title":"The sedative component of anesthesia is mediated by GABAA receptors in an endogenous sleep pathway","volume":"5","author":"Nelson","year":"2002","journal-title":"Nature Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1097\/00000542-200512000-00024","article-title":"Sleep, Anesthesiology, and the Neurobiology of Arousal State Control","volume":"103","author":"Lydic","year":"2005","journal-title":"Anesthesiology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1038\/nrn2372","article-title":"General anaesthesia: From molecular targets to neuronal pathways of sleep and arousal","volume":"9","author":"Franks","year":"2008","journal-title":"Nature Rev. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/j.cub.2019.12.063","article-title":"Activation of preoptic GABAergic or glutamatergic neurons modulates sleep-wake architecture but not anesthetic state transitions","volume":"30","author":"Vanini","year":"2020","journal-title":"Curr. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"FSO664","DOI":"10.2144\/fsoa-2020-0149","article-title":"Differences between natural sleep and the anesthetic state","volume":"6","author":"Date","year":"2020","journal-title":"Future Sci. OA"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Solpata, A.E., McCarthy, M.M., Sherfey, J., Lee, S., Purdon, P.L., Brown, E.N., and Kopell, N. (2017). Thalamocortical control of propofol phase-amplitude coupling. PLoS Comput. Biol., 13.","DOI":"10.1371\/journal.pcbi.1005879"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.bja.2020.05.031","article-title":"Resistance to state in responsiveness is differentially modulated by different volatile anaesthetics in male mice","volume":"125","author":"Wasilczuk","year":"2020","journal-title":"Br. J. Anaesth."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1097\/01.anes.0000270734.99298.b4","article-title":"Differential dynamic of action on cortical and subcortical structures of anesthetic agents during induction of anesthesia","volume":"107","author":"Velly","year":"2007","journal-title":"Anesthesiology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/S0166-2236(00)02002-6","article-title":"The sleep switch: Hypothalamic control of sleep and wakefulness","volume":"24","author":"Saper","year":"2001","journal-title":"Trends Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/nature04767","article-title":"A putative flip-flop switch for control of REM sleep","volume":"441","author":"Lu","year":"2006","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1097\/00000542-200210000-00024","article-title":"Sleep deprivation potentiates the onset and duration of loss of righting reflex induced by propofol and isoflurane","volume":"97","author":"Tung","year":"2002","journal-title":"Anesthesiology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1097\/00000539-200105000-00028","article-title":"Prolonged sedation with propofol in the rat does not result in sleep deprivation","volume":"92","author":"Tung","year":"2001","journal-title":"Anesth. Analg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1053\/smrv.2001.0170","article-title":"Brain structures and mechanisms involved in the generation of NREM sleep: Focus on the preoptic hypothalamus","volume":"5","author":"McGinty","year":"2001","journal-title":"Sleep Med. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s40140-012-0007-0","article-title":"Sleep and anesthesia interactions: A pharmacological appraisal","volume":"3","author":"Scharf","year":"2013","journal-title":"Curr. Anesthesiol. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1002\/1096-9861(20010122)429:4<638::AID-CNE10>3.0.CO;2-Y","article-title":"Subregional organization of preoptic area\/anterior hypothalamic projections to arousal-related monoaminergic cell groups","volume":"429","author":"Steininger","year":"2001","journal-title":"J. Comp. Neurol."},{"key":"ref_16","first-page":"77","article-title":"Preoptic area sleep-regulating mechanisms","volume":"139","author":"Szymusiak","year":"2001","journal-title":"Arch. Ital. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.conb.2017.03.021","article-title":"Wake-sleep circuitry: An overview","volume":"44","author":"Saper","year":"2017","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1016\/j.cub.2012.08.042","article-title":"Direct activation of sleep-promoting VLPO neurons by volatile anesthetics contributes to anesthetics hypnosis","volume":"22","author":"Moore","year":"2012","journal-title":"Curr. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1152\/physrev.00032.2011","article-title":"Control of sleep and wakefulness","volume":"92","author":"Brown","year":"2012","journal-title":"Physiol. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1523\/JNEUROSCI.23-03-00876.2003","article-title":"Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistant learning deficits","volume":"23","author":"Hartman","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.anclin.2015.05.008","article-title":"Postoperative cognitive dysfunction, minding the gaps in our knowledge of a common postoperative complications in the elderly","volume":"33","author":"Berger","year":"2015","journal-title":"Anesthesiol. Clin."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Sleigh, J.W., Voss, I., Steyn-Ross, M.I., Steyn-Ross, D.A., and Wilson, M.T. (2011). Modeling Sleep and General Anesthesia in Sleep and Anesthesia, Springer.","DOI":"10.1007\/978-1-4614-0173-5_2"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1097\/ACO.0000000000000790","article-title":"Anesthesia-induced immune modulation","volume":"32","author":"Rossaint","year":"2019","journal-title":"Curr. Opin. Anesthesiol."},{"key":"ref_24","first-page":"224","article-title":"A review of nausea and vomiting in the anesthetic and post anesthetic environment","volume":"27","author":"Matthews","year":"2017","journal-title":"J. Perioper. Pract."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1111\/vaa.12216","article-title":"Anaesthetic and cardiorespiratory effects of a constant rate infusion of fentanyl in isoflurane-anaesthetized sheep","volume":"42","author":"Funes","year":"2015","journal-title":"Vet. Anaesth. Analg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"50","DOI":"10.3389\/fnins.2019.00576","article-title":"Regulation of local sleep by the thalamic reticular nucleus","volume":"13","author":"Vantomme","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1097\/00000542-200402000-00018","article-title":"An investigation to dissociate the analgesic and anesthetic properties of ketamine using functional magnetic resonance imaging","volume":"100","author":"Rogers","year":"2004","journal-title":"Anesthesiology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1002\/cne.21685","article-title":"Role of endogenous sleep-wake and analgesic system in anesthesia","volume":"508","author":"Lu","year":"2008","journal-title":"J. Comp. Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1111\/j.1476-5381.1983.tb11031.x","article-title":"The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurons by N-methyl-aspartate","volume":"79","author":"Anis","year":"1983","journal-title":"Br. J. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2638","DOI":"10.1056\/NEJMra0808281","article-title":"General anesthesia, sleep and coma","volume":"363","author":"Brown","year":"2010","journal-title":"N. Engl. J. Med"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1097\/ALN.0b013e31823d010a","article-title":"Ketamine activates breathing and abolishes the coupling between loss of consciousness and upper airway dilator muscle dysfunction","volume":"116","author":"Eikermann","year":"2012","journal-title":"Anesthesiology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1093\/bja\/77.3.381","article-title":"Differential effects of ketamine and pentobarbitone on acetylcholine release from the rat hippocampus and striatum","volume":"77","author":"Sato","year":"1996","journal-title":"Br. J. Anaesth."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1093\/bja\/74.1.79","article-title":"Selective effects of ketamine on amino acid-mediated pathwys in neonatal rat spinal cord","volume":"74","author":"Brockmeyer","year":"1995","journal-title":"Br. J. Anaesth."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0006-8993(99)01793-X","article-title":"Physostigmine antagonizes ketamine-induced noradrenaline release from the medial prefrontal cortex in rats","volume":"840","author":"Kubota","year":"1999","journal-title":"Brain Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1142\/S0218348X1100521X","article-title":"Different anesthesia in rat induces distinct inter-structure brain dynamics detected by Higuchi fractal dimension","volume":"19","author":"Spasic","year":"2011","journal-title":"Fractals"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"E6660","DOI":"10.1073\/pnas.1700148114","article-title":"Thalamocortical synchronization during induction and emergence from propofol-induced unconsciousness","volume":"114","author":"Flores","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"22665","DOI":"10.1073\/pnas.1017069108","article-title":"Thalamocortical model for a propofol-induced alpha-rhythm associated with loss of consciousness","volume":"107","author":"Ching","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"fcac010","DOI":"10.1093\/braincomms\/fcac010","article-title":"Dysfunction of parvalbumin-expressing cells in the thalamic reticular nucleus induces cortical spike-and-wave discharges and an unconscious state","volume":"4","author":"Abdelaal","year":"2022","journal-title":"Brain Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1126\/science.8235588","article-title":"Thalamocortical oscillations in the sleeping and aroused brain","volume":"262","author":"Steriade","year":"1993","journal-title":"Science"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/nature17427","article-title":"Thalamic reticular impairment underlies attention deficit in Ptchd1Y\/- mice","volume":"532","author":"Wells","year":"2016","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/nm.2330","article-title":"GIT1 is associated with ADHD in humans and ADHD-like behaviors in mice","volume":"17","author":"Won","year":"2011","journal-title":"Nat. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/0887-8994(92)90049-5","article-title":"Quantitative analysis of EEG in boys with attention-deficit-hyperactivity disorder: Controlled stdy with clinical implications","volume":"8","author":"Mann","year":"1992","journal-title":"Pediatr Neurol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"112957","DOI":"10.1016\/j.bbr.2020.112957","article-title":"Prodromal local sleep disorders in a rat model of Parkinson\u2019s disease cholinopathy, hemiparkinsonism and hemiparkinsonism with cholinopathy","volume":"397","author":"Petrovic","year":"2021","journal-title":"Behav. Brain Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e13090","DOI":"10.1111\/jsr.13090","article-title":"Diversity of simultaneous sleep in the motor cortex and hippocampus in rats","volume":"30","author":"Petrovic","year":"2021","journal-title":"J. Sleep Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/j.expneurol.2013.02.007","article-title":"Lesion of the pedunculopontine tegmental nucleus in rat augments cortical activation and disturbs sleep\/wake state transitions structure","volume":"247","author":"Petrovic","year":"2013","journal-title":"Exp. Neurol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Radovanovic, L., Petrovic, J., and Saponjic, J. (2021). Hippocampal and Reticulo-Thalamic Parvalbumin Interneurons and Synaptic Re-Organization during Sleep Disorders in the Rat Models of Parkinson\u2019s Disease Neuropathology. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168922"},{"key":"ref_47","unstructured":"Paxinos, G., and Watson, C. (2005). The Rat Brain in Stereotaxic Coordinates, Academic Press. [5th ed.]."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Dorszewska, J., and Kozubski, W. (2016). Challenges in Parkinson\u2019s Disease, InTech Rijeka.","DOI":"10.5772\/61880"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1111\/sbr.12011","article-title":"Sleep-state related EEG amplitude distribution in the rat model of cortical cholinergic innervation disorder","volume":"11","author":"Saponjic","year":"2013","journal-title":"Sleep Biol. Rhythms"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"103482","DOI":"10.1016\/j.compbiomed.2019.103482","article-title":"Novel application of the gray-level.co-occurrence matrix analysis in the parvalbumin stained hippocampal gyrus dentatus in distinct rat models of Parkinson\u2019s disease","volume":"115","author":"Rajkovic","year":"2019","journal-title":"Comput. Biol. Med."},{"key":"ref_51","unstructured":"Paxinos, G., Watson, C., Carrive, P., Kirkcaldie, M., and Ashwell, K.W.S. (2009). Chemoarchitectonic Atlas of the Rat Brain, Academic Press. [2nd ed.]."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/7\/6769\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:10:18Z","timestamp":1760123418000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/7\/6769"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,5]]},"references-count":51,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["ijms24076769"],"URL":"https:\/\/doi.org\/10.3390\/ijms24076769","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,5]]}}}