Neurobiology of Sleep Lab, University of Belgrade

Institute for Biological Res - Sinisa Stankovic

Jasna Saponjic
Research Professor
Despot Stefan Blvd. 142
+381 11 2078426
+381 11 2761433
Research Domain
  • Basic Animal
  • Neurological Sleep Disorders
  • Behavioural Sleep Disorders
  • Biological Rhythms
  • Sleep Physiology-Neurophysiology in Animal

Laboratory description

Our current research focuses on the neurobiology of sleep and sleep-related breathing in the animal models “in vivo” of healthy aging and neuropathology of the most common neurodegenerative diseases of elderly (Alzheimer’s Disease (AD), Parkinson’s Disease (PD), different types of dementia), aimed to give a new insight into understanding of normal and abnormal sleep, the mechanisms of sleep related behavioural disorders, particularly sleep apnea syndrome, and to identify the neural networks responsible for modifying the regulation of sleep and breathing pattern in different sleep/wake states.

Since underlying pathology of AD and PD involves the selective loss of specific neuronal population, an important role of the cholinergic system in their etiology, and the ascending pattern of neurodegeneration progression, from REM sleep-related brainstem regulatory structures to basal areas of the brain, in our research we use the rat models of unilateral or bilateral lesion of the nucleus basalis (NB; the main cortical cholinergic nucleus), and nucleus pedunculopontine tegmentum, (PPT; the main cholinergic nucleus of the brainstem – pons) as the experimental models of brain functionally distinct cholinergic neuropathology.

We follow the severity and progression of disorder caused by neurodegenerative process by electroencephalography (EEG) and electromyography (EMG): by the changes of sleep/wake states and NREM/REM cycling, EEG rhythms or EEG oscillations. We correlate all changes within EEG with the changes in breathing pattern using the methods of linear and nonlinear analysis to estimate the onset, progression, and severity of the disorder. We believe that EEG potentially presents a rich source of still unrevealed information related to functional, physiological, and pathological status of the brain. Developing the new methods for EEG processing and modelling will significantly contribute in understanding the mechanisms of sleep regulation, detection of disease related sleep and sleep-related breathing disorders, and in estimation of the neurodegenerative disease progression.

Complementary studies in the animal models of human neurodegenerative pathology will highly enrich the development of practical, sensitive and reliable methodology for early detection of the sleep behavioural disordered patients, who are at risk for developing Alzheimer’s and Parkinson’s Disease, or for the prevention and alteration of approaches for therapy.

Key Publications of the Laboratory:

  1. Ciric J, Kapor S, Perovic M, Saponjic J. Alterations of Sleep and Sleep Oscillations in the Hemiparkinsonian Rat. Frontiers in Neuroscience 2019, 13: Article 148.

  2. Lazic K, Ciric J, Saponjic J. Sleep spindle dynamics during NREM and REM sleep following distinct general anaesthesia in control rats and in a rat model of Parkinson’s disease cholinopathy. Journal of Sleep Research 2019; 28: e12758.

  3. Ciric j, Lazic K, Kapor S, Perovic M, Petrovic J, Pesic J, Pesic V, Kanazir S, Saponjic J. Sleep disorder and altered locomotor activity as biomarkers of the Parkinson’s disease cholinopathy in rat. Behavioural Brain Research 2018; 339: 79-92.

  4. Petrovic J, Milosevic V, Zivnovic M, Stojanov D, Milojkovic O, Kalauzi A, Saponjic J. Slower EEG alpha generation, synchronization and “flow” – possible biomarkers of cognitive impairment and neuropathology of minor stroke. PeerJ, 2017; 9, art. No e-3839.

  5. Ciric J, Layic K, Petrovic J, Kalauzi A, Saponjic J. Sleep spindles as an early biomarker of REM sleep disorder in a rat model of Parkinson’s disease cholinopathy. Translational Brain Rhythmicity 2017; 2: 1-11.

  6. Ciric J, Lazic K., Petrovic J., Kalauzi A., Saponjic J. Age-related disorders of sleep and motor control in the rat models of functionally distinctcholinergic neuropathology. Behavioural Brain Research, 2016; 301:273-286. 

  7. Lazic K, Petrovic J, Ciric J, Kalauzi A, Saponjic J. Impact of anesthetic regimen on the respiratory pattern, EEG microstructure and sleep in the rat model of cholinergic Parkinson's disease neuropathology. Neuroscience 2015; 304:1-13.

  8. Ciric J, Lazic K, Petrovic J, Kalauzi A, Saponjic J. Aging induced cortical drive alterations during sleep in rats. Mechanisms of Ageing and Development 2015;146-148:12-22.

  9. Bataveljic D, Petrovic J, Lazic K, Saponjic J, Andjus P. Glial response in the rat models of functionally distinct cholinergic neuronal denervations. Journal of Neuroscience Research 2015; 93:244-252.

  10. Petrovic J, Lazic K, Kalauzi A, Saponjic J. REM sleep diversity following the pedunculopontine tegmental nucleus lesion in rat. Behavioural Brain Research 2014; 271:258-268.

  11. Bjelobaba I, Saponjic J. High volume microinjection suppresses local astrocyte response within nucleus basalis of rat. Archives Italiennes de Biologie. 2013;151:24-32.

  12. Petrovic J, Lazic K, Ciric J, Kalauzi A, Saponjic J. Topography of the sleep/wake states related EEG microstructure and transitions structure differentiates the functionally distinct cholinergic innervation disorders in rat. Behavioural Brain Research 2013; 256:108-118.

  13. Petrovic J, Ciric J, Lazic K, Kalauzi A, Saponjic J. Lesion of the pedunculopontine tegmental nucleus in rat augments cortical activation and disturbs sleep/wake state transitions structure. Experimental Neurology 2013; 247:562-571.

  14. Saponjic J, Petrovic J, Kalauzi A, Ciric J, Lazic K, Radulovcki M, Carley DW. Sleep-state related EEG amplitude distribution in the rat model of cortical cholinergic innervation disorder. Sleep and Biological Rhythms 2013; 11:105-115.

  15. Kalauzi A, Spasic S, Petrovic J, Ciric J, Saponjic J. Cortico-pontine theta carrier frequency phase shift across sleep/wake states following monoaminergic lesion in rat. General Physiology and Biophysics 2012;31(2):163-171.

  16. Spasic S, Kesic S, Kalauzi A, Saponjic J. Different anesthesia in rat induces distinct inter-structure brain dynamic detected by Higuchi fractal dimension, Fractals – Complex Geometry, Patterns, and Scaling in Nature and Society 2011; 19(1):113-123.

  17. Spasic S, Kalauzi A, Kesic S, Obradovic M, Saponjic J. Surrogate data modeling the relationship between high frequency amplitudes and Highuchi fractal dimension of EEG signals in anesthetized rats, Journal of Theoretical Biology, 2011; 289:160-166.

  18. Kesic S, Kalauzi A, Radulovacki M, Carley DW, Saponjic J. Coupling changes in cortical and pontine sigma and theta frequency oscillations following monoaminergic lesions in rat. Sleep and Breathing 2011; 15(1):35-47.

  19. Kalauzi A, Kesic S, Saponjic J. Cortico-pontine theta synchronization phase shift following monoaminergic lesion in rat, Journal of Physiology and Pharmacology 2009; 60(4): 79-84.

  20. Bojic T, Saponjic J, Radulovacki M, Carley WD, Kalauzi A. Monotone signal segments analysis as a novel method of breath detection and breath-to-breath interval analusis in rat. Respiratory Physiology & Neurobiology 2008;161:273-280.

  21. Saponjic J, Radulovacki M, Carley DW. Monoaminergic system lesions increase post-sigh respiratory pattern disturbance during sleep in rats. Physiology & Behavior 2007; 90:1-10.

  22. Radulovacki M, Stoiljkovic M, Saponjic J, Carley DW. Effects of Intratrigeminal Region NMDA and non-NMDA Receptors on Respiratory Responses in Rats. Respiratory Physiology & Neurobiology 2007; 156:40-46.

  23. Saponjic J, Radulovacki M, Carley DW. Modulation of respiratory pattern and upper airway muscle activity by the pedunculopontine tegmentum: Role of NMDA receptors, Sleep & Breathing 2006; 10:195-202.

  24. Saponjic J, Radulovacki M, Carley DW. Injection of glutamate into the pedunculopontine tegmental nuclei of anesthetized rat causes respiratory dysrhythmia and alters EEG and EMG power. Sleep & Breathing 2005; 9:82-91.

  25. Saponjic J, Cvorovic J, Radulovacki M, Carley DW. Serotonin and noradrenaline modulate respiratory pattern disturbance evoked by glutamate injection into pedunculopontine tegmentum of anesthetized rats. Sleep 2005; 28(5):560-570.

  26. Radulovacki M, Pavlovic S, Saponjic J, Carley DW. Modulation of reflex and sleep related apnea by pedunculopontine tegmental and intertrigeminal neurons. Respiratory Physiology & Neurobiology 2004; Review, 143:293-306.

  27. Carley DW, Pavlovic S, Malis M, Knezevic N, Saponjic J, Li C, Radulovacki M. C-fiber activation exarcerbates sleep-disordered breathing in rats. Sleep & Breathing 2004; 8:147-154.

  28. Saponjic J, Radulovacki M, Carley DW. Respiratory pattern modulation by the pedunculopontine tegmental nucleus. Respiratory Physiology & Neurobiology 2003; 138:223-237.

  29. Radulovacki M, Pavlovic S, Saponjic J, Carley DW. Intertrigeminal region attenuates reflex apnea and stabilizes respiratory pattern in rats. Brain Research 2003; 975:66-72.

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