Integrated Physiology of Brain Arousal Systems, INSERM-CNRS-UCBL1

Lyon Neuroscience Research Center (CRNL)

Jian-Sheng Lin
Director of Research
8 avenue Rockefeller, 69373
+33 (0)478777041
+33 (0)478777150
Contact E-mail:
Research Domain

Laboratory description

Our goal is to unravel the mechanisms of wake and associated pathologies: narcolepsy, excessive daytime sleepiness, insomnia, metabolic disorders, sudden infant death syndrome.

From a basic research standpoint, we dissect the mechanisms of wake through the study of the specific, complementary and synergistic roles of histaminergic and orexinergic neurons in particular. Using specific knock out mice and detailed behavioural and electroencephalographic measures, we will determine how the two systems interact synergistically and integrate into the central mechanisms of arousal. We also use intracellular recordings, local field potentials and biosensors to study the properties of the cortical network during different types of wake, the respective role of diffuse ascending systems and specific cerebral nuclei, and the mechanisms and effects of extra-synaptic variations of neurotransmitter (glutamate, histamine, D-serine).

From a physio-pathological and translational research standpoint, we work on 1) developing therapeutic approaches for narcolepsy and excessive daytime sleepiness using our knowledge of histaminergic and orexinergic systems, 2) investigating the interactions between sleep loss and metabolic disorders in lean subjects and obese patients and in animal models combining sleep/wake and metabolic alterations, and 3) identifying new signalling pathways and biomarkers associated with wake thanks to Drosophila molecular genetics and an insomnia model in this organism.

Technical Capabilities and areas of expertise

Electrophysiology both in human and in the animal (EEG, local field potential, intra and extracellular recordings), Polysomnography,
Electrochemistry (biosensors),
Neuro-behavioural testing,
Cognitive, metabolic and endocrine testing in human
Animal models for sleep disorders
Sleep Molecular genetics in Drosophila

Additional Descriptors, Keywords

wake, sleep disorders, inegrated physiology, metabolism, molecular genetics, biosensor sleep medicine

Selected Publications in the 5 past years:

Check also our website for more information

1. Takahashi K Lin JS Sakai K, 2006, Neuronal activity of histaminergic tuberomammillary neurons during wake-sleep states in the mouse. J Neurosci, 26 (40): 10292-8.

2. Seugnet L Botero J Gottschalk L Duntley SP Shaw PJ, 2006 Identification of a biomarker for sleep drive in flies and humans. PNAS, 103, 19913-8.

3. Anaclet C, Parmentier R, Ouk K, Guidon G, Buda C, Sastre JP, Akaoka H, Sergeeva OA, Yanagisawa M, Ohtsu H, Franco P, Haas HL, Lin JS (2009) Orexin/hypocretin and histamine: distinct roles in the control of wakefulness demonstrated using knock-out mouse models. J Neurosci 29:14423-14438.

4. Guo RX, Anaclet C, Roberts JC, Parmentier R, Zhang M, Guidon G, Buda C, Sastre JP, Feng JQ, Franco P, Brown SH, Upton N, Medhurst AD, Lin JS (2009) Differential effects of acute and repeat dosing with the H3 antagonist GSK189254 on the sleep-wake cycle and narcoleptic episodes in Ox-/- mice. Br J Pharmacol 157:104-117.

5. Parmentier R, Kolbaev S, Klyuch BP, Vandael D, Lin JS, Selbach O, Haas HL, Sergeeva OA (2009) Excitation of histaminergic tuberomamillary neurons by thyrotropin-releasing hormone. J Neurosci 29:4471-4483.

6. Seugnet L, Suzuki Y, Thimgan M, Donlea J, Gimbel SI, Gottschalk L, Duntley SP, Shaw PJ (2009c) Identifying sleep regulatory genes using a Drosophila model of insomnia. J Neurosci 29:7148-7157.

7. Spiegel K, Tasali E, Leproult R, Van Cauter E (2009) Effects of poor and short sleep on glucose metabolism and obesity risk. Nat Rev Endocrinol 5:253-261.

8. Gentet LJ, Avermann M, Matyas F, Staiger JF, Petersen CC (2010) Membrane potential dynamics of GABAergic neurons in the barrel cortex of behaving mice. Neuron, 2010 65(3):422-435.

9. Lin JS, Sergeeva OA, Haas HL (2010) Histamine H3-receptors and sleep-wake regulation. J Pharmacol Exp Ther. 336(1)17-23, 2011

10. Sakai K, Takahashi K, Anaclet C, Lin JS (2010) Sleep-waking discharge of ventral tuberomammillary neurons in wild-type and histidine decarboxylase knock-out mice. Front Behav Neurosci 4:53. Gentet LJ, Avermann M, Matyas F, Staiger JF, Petersen CC (2010) Membrane potential dynamics of GABAergic neurons in the barrel cortex of behaving mice. Neuron, 2010 65(3):422-435.

11. Spiegel K, Tasali E, Leproult R, Scherberg N, Van Cauter E (2010) Twenty-Four-Hour Profiles of Acylated and Total Ghrelin: Relationship with Glucose Levels and Impact of Time of Day and Sleep. J Clin Endocrinol Metab.

12. Crochet S, Poulet JF, Kremer Y, Petersen CC (2011) Synaptic mechanisms underlying sparse coding of active touch. Neuron, 69, p 1160-1175

13. Franco P, Montemitro E, Scaillet S, Groswasser J, Kato I, Lin JS, Villa MP (2011a) Fewer spontaneous arousals in infants with apparent life-threatening event. Sleep 34:733-743.

14. Lin JS, Anaclet C, Sergeeva OA, Haas HL (2011) The waking brain: an update. Cell Mol Life Sci.

15. Neuzeret PC, Gormand F, Reix P, Parrot S, Sastre JP, Buda C, Guidon G, Sakai K, Lin JS (2011) A new animal model of obstructive sleep apnea responding to continuous positive airway pressure. Sleep 34:541-548.

16. Seugnet L, Suzuki Y, Merlin G, Gottschalk L, Duntley SP, Shaw PJ (2011b) Notch signaling modulates sleep homeostasis and learning after sleep deprivation in Drosophila. Curr Biol 21:835-840.

17. Vasylieva N, Barnych B, Meiller A, Maucler C, Pollegioni L, Lin JS, Barbier D, Marinesco S (2011) Covalent enzyme immobilization by poly(ethylene glycol) diglycidyl ether (PEGDE) for microelectrode biosensor preparation. Biosens Bioelectron.

18. Yanovsky Y, Li S, Klyuch BP, Yao Q, Blandina P, Passani MB, Lin JS, Haas HL, Sergeeva OA (2011) L-Dopa activates histaminergic neurons. J Physiol Paris 589:1349-1366.

19. Anaclet C, Lin JS, Vetrivelan R, Krenzer M, Vong L, Fuller PM, Lu J (2012a) Identification and characterization of a sleep-active cell group in the rostral medullary brainstem. J Neurosci 32:17970-17976.

20. Anaclet C, Zhang M, Zhao C, Buda C, Seugnet L, Lin JS (2012b) Effects of GF-015535-00, a Novel alpha1 GABA(A) Receptor Ligand, on the Sleep-Wake Cycle in Mice, with Reference to Zolpidem. Sleep 35:103-111.

21. Aznavour N, Cendres-Bozzi C, Lemoine L, Buda C, Sastre JP, Mincheva Z, Zimmer L, Lin JS (2012) MPTP animal model of Parkinsonism: dopamine cell death or only tyrosine hydroxylase impairment? A study using PET imaging, autoradiography, and immunohistochemistry in the cat. CNS Neurosci Ther 18:934-941.

22. Crochet S*, Fernandez LM*, Poulet JF* Petersen CC (2012) Thalamic control of cortical states. Nat Neurosci 15:370-372. * equal contribution

23. Gentet LJ, Kremer Y, Taniguchi H, Huang ZJ, Staiger JF, Petersen CC (2012) Unique functional properties of somatostatin-expressing GABAergic neurons in mouse barrel cortex. Nat Neurosci 15:607-612.

24. Inocente CO, Arnulf I, Bastuji H, Thibault-Stoll A, Raoux A, Reimao R, Lin JS, Franco P (2012) Pitolisant, an Inverse Agonist of the Histamine H3 Receptor: An Alternative Stimulant for Narcolepsy-Cataplexy in Teenagers With Refractory Sleepiness. Clin Neuropharmacol 35:55-60.

25. Morselli LL, Guyon A, Spiegel K (2012) Sleep and metabolic function. Pflug Arch Eur J Phys 463:139-160.

26. Onen SH, Lesourd B, Ouchchane L, Lin JS, Dubray C, Gooneratne NS, Onen F (2012) Occult nighttime hypertension in daytime normotensive older patients with obstructive sleep apnea. J Am Med Dir Assoc 13:752-756.

27. Gondard E, Anaclet C, Akaoka H, Guo RX, Zhang M, Buda C, Franco P, Kotani H, Lin JS (2013) Enhanced Histaminergic Neurotransmission and Sleep-Wake Alterations, a Study in Histamine H3-Receptor Knock-Out Mice. Neuropsychopharmacology. 2013,38(6):1015-31

28. Inocente CO, Lavault S, Lecendreux M, Dauvilliers Y, Reimao R, Gustin MP, Castets S, Spiegel K, Lin JS, Arnulf I, Franco P (2013) Impact of obesity in children with narcolepsy. CNS Neurosci Ther 19:521-528.

Other laboratory Members

Title:  PhD

Name:  Karine Spiegel


Title:  PhD

Name:  Luc Gentet


Title:  PhD

Name:  Stephane Marinesco


Title:  PhD

Name:  Kasuya Sakai


Title:  PhD

Name:  Laurent Seugnet


Title:  PhD MD

Name:  Patricia Franco


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