Chronobiology and affective disorders
The research aims of Neurobiological Rhythms and Sleep are focused on the molecular, cellular and behavioral mechanisms of the circadian timing system and the consequences of aging and neurodegenerative disease. Central to our approach is an understanding of the synchronization of circadian rhythms by the external light cycle, the molecular and physiological mechanisms of the endogenous circadian oscillator (SCN), and the regulation of output behavioral and physiological rhythms. The coding of photic information by retinal photoreceptors (rods, cones, melanopsin ganglion cells) are studied using in vivo electrophysiological recording techniques in anaesthetised and awake, freely moving animals. The effects of light (intensity, duration, spectrum) on SCN neuronal activity and on clock gene expression are also assayed using quantitative RT-PCR, laser dissection and microarray analysis. In order to understand the consequences of chronobiological disorders, another line of research involves investigation of the mechanisms of synchronisation of central and peripheral oscillators, including the expression of clock genes and rhythmically expressed clock controlled genes in the brain and in different body tissues. Pathological models investigated in rodents include ocular diseases and Parkinson's disease, and a prosimian primate model of aging. In humans, circadian photoreception and entrainment of the circadian timing system as well as chronobiological disorders related to ocular pathologies, aging and neurodegenerative diseases are studied in the framework of a European integrated project in our clinically based Platform for Research on Human Chronobiology. In order to bridge the gap between cellular-molecular studies in rodent models and clinical studies in humans, the non-human primate is used to study the circadian timing system and sleep wake cycle and, in the framework of the laboratory transversal project, the chronobiological consequences of Parkinson's Disease.
|Dr. Howard Cooper || |
The research aims of Neurobiological Rhythms and Sleep are focused on the molecular, cellular and behavioral mechanisms of the circadian timing system and the consequences of aging and neurodegenerative disease.Our approaches strive to understand the mechanisms of synchronization of circadian rhythms by lignt, the molecular and physiological mechanisms of the endogenous circadian oscillators, and the regulation of output behavioral and physiological rhythms. The coding of photic information ...
| Nasser Haddjeri || |
Since 20 years, my research focuses on the neurobiology of mood disorders and their responses to antidepressant treatments. A main goal is to understand the neural bases associated to the antidepressant responses in order to develop novel therapeutics for affective disorders. My work particularly focus on gaining a clearer understanding of the physiology and pharmacology of brain monoamine neurotransmitters and how these neurotransmitter systems are affected by established ...
| Hugo Calligaro || |
My PhD project focuses on understanding how the mammalian retinal clock
is entrained by light. I aim first to explore the molecular mechanisms
underlying light entrainment of the retinal clock, especially the role
of dopamine and the relative contributions of the different
photoreceptors in these processes. Second, I will determine whether the
absence of specific photoreceptors contributes to retinal clock
dysfunction. Several complementary approaches ...
| Christine Coutanson || |
| Sarah Delcourte PhD Student|| |
| Ouria Dkhissi-Benyahya || |
My research interest is to understand how the circadian system is regulated by light, the role of classical and novel photoreceptors in circadian light perception and the consequences of specific photoreceptor deletions on the functioning of the retinal oscillator and the central endogenous clock. This work include a range of molecular, cellular, anatomical and behavioral approaches.
| Claude Gronfier || |
My research focuses on how light synchronizes physiology, including the circadian timing system, to the 24h day in humans. My projects investigate the mechanisms involved in non-visual photoreception, the effects of light on physiological functions (alertness, cognition, mood), and how light could be used/designed to treat circadian, mood, vigilance, and sleep disorders, in shiftwork and pathological conditions (Ocular diseases, neurodegenerative ...
| Chaimaa Kinane || |
My work aims to determine the ontogeny of the endogenous molecular machinery of the mammalian retinal clock. I will also explore when during the development, the retinal clock begin to respond to light and the relative contributions of the different photoreceptors in this response using in vivo and in vitro approaches in photoreceptor-deficient mice.
| Abhishek Prayag || |
My current research interests lies in deciphering the contribution of the rods, cones and melanopsin-ganglion cells in the computation of non-visual responses at the level of the human brain. At the retinal interface, signals coming from the classical photoreceptors and melanopsin cells interact to elicit a wide range of responses in the brain, including crucially: the circadian system, sleep architecture, temperature regulation, hormonal levels, cognitive performance ...
| Renaud Rovera || |
In vivo electrophysiological and behavioral techniques.
| Hélène Scarna || |
My research interest focus on clinical observations of depression states in the field of addiction and trying to highlight neurobiological knowledges of these psychopathologies. On the other hand, rodent models of these diseases and behavioral approach permit us to test psychotropic drugs as potential medecine.
Selected Publications of Team members : |
Raymond P. Najjar; Petteri Teikari; Pierre-Loïc Cornut; Kenneth Knoblauch; Howard M. Cooper; Claude Gronfier (2016) Heterochromatic Flicker Photometry for Objective Lens Density Quantification Investigative Ophthalmology & Visual Science March 2016, Vol.57, 1063-1071. doi:10.1167/iovs.15-18642
Bétry C, Overstreet D, Haddjeri N, Pehrson AL, Bundgaard C, Sanchez C, Mørk A (2015) A 5-HT3 receptor antagonist potentiates the behavioral, neurochemical and electrophysiological actions of an SSRI antidepressant Pharmacol Biochem Behav. 2015 Apr;131:136-42
Wright KP Jr, Drake AL, Frey DJ, Fleshner M, Desouza CA, Gronfier C and Czeisler CA (2015) Influence of sleep deprivation and circadian misalignment on cortisol, inflammatory markers, and cytokine balance Brain Behav Immun. 2015 Jul;47:24-34
A. Etiévant, C. Oosterhof, C. Bétry, E. Abrial, M. Novo-Perez, R. Rovera, H. Scarna, C. Devader, J. Mazella, G. Wegener, C. Sánchez, O. Dkhissi-Benyahya, C. Gronfier, V. Coizet, J.M. Beaulieu, P. Blier, G. Lucas, N. Haddjeri (2015) Astroglial control of the antidepressant-like effects of prefrontal cortex deep brain stimulation EbioMedecine. 2(8):896-906
Bétry C, Etiévant A, Pehrson A, Sánchez C, Haddjeri N (2015) Effect of the multimodal acting antidepressant vortioxetine on rat hippocampal plasticity and recognition memory Prog Neuropsychopharmacol Biol Psychiatry. 2015 Apr 3;58:38-46
Westrich L, Haddjeri N, Dkhissi-Benyahya O, Sánchez C (2015) Involvement of 5-HT₇ receptors in vortioxetine's modulation of circadian rhythms and episodic memory in rodents Neuropharmacology. 2015; 89:382-90
Najjar RP, Chiquet C, Teikari P, Cornut PL, Claustrat B, Denis P, Cooper HM, Gronfier C (2014) Aging of Non-Visual Spectral Sensitivity to Light in Humans: Compensatory Mechanisms? Plos One, 9(1): e85837 download
Fifel K, Vezoli J, Dzahini K, Claustrat B, Leviel V, Kennedy H, Procyk E, Dkhissi-Benyahya O, Gronfier C, Cooper HM (2014) Alteration of daily and circadian rhytms following dopamine depletion in MPTP treated Non-Human Primates. PLoS One, 2014, 9(1):e86240
Chellappaa SL, Lya JQM, Meyera C, Balteaua E, Degueldrea C, Luxena A, Phillipsa C, Cooper HM, Vandewallea G (2014) Photic memory for executive brain responses PNAS, 111(16): 6087-91
Najjar R.P., Wolf L, Taillard J, Schlangen L., Salam A, Cajochen C, Gronfier C (2014) Chronic artificial blue-enriched white light is an effective countermeasure to delayed circadian phase and neurobehavioral decrements. Plos One, 9:e102827
Abrial E, Bétourné E, Etiévant A, Lucas G, Scarna H, Lambás-Señas L, Haddjeri N (2014) Protein kinase C inhibition rescues manic-like behaviors and hippocampal cell proliferation deficits in the sleep deprivation model of mania. Int J Neuropsychopharmacol, in press.
Lahouaoui H, Coutanson C, Cooper HM, Bennis M, Dkhissi-Benyahya O (2014) Clock genes and behavioral responses to light are altered in a mouse model of diabetic retinopathy. PLoS One 9(7):e101584
Dkhissi-Benyahya O, Coutanson C, Knoblauch K, Lahouaoui H, Leviel V, Rey C, Bennis M, Cooper HM. (2013) The absence of melanopsin alters retinal clock function and dopamine regulation by light. Cell Mol Life Sci. 3435-3447
Abrial E, Etiévant A, Bétry C, Scarna H, Lucas G, Haddjeri N, Lambás-Señas L (2013) Protein kinase C regulates mood-related behaviors and adult hippocampal cell proliferation in rats. Prog Neuro-Psychopharmacol Biol Psychiatry, 43(3): 40–48
Fifel K, Dkhissi-Benyahya O, Cooper HM (2013) Lack of long term changes in circadian, motor and cognitive functions in acute and chronic MPTP mouse models of Parkinson’s disease. Chronobiol Int, 30(6): 741–755
Ritzenthaler T, Lhommeau I, Douillard S, Cho TH, Brun J, Patrice T, Nighoghossian N, Claustrat B (2013) Dynamics of oxidative stress and urinary excretion of melatonin and its metabolites during acute ischemic stroke. Neurosci Lett, 544:1-4
Betry C, Etievant A, Ebert B, Pehrson A, Sánchez C, Haddjeri N (2013) The rapid recovery of 5-HT cell firing induced by the antidepressant vortioxetine involves 5-HT3 receptor antagonism. International Journal of Neuropsychopharmacology. 16(5):1115-1127.
Teikari P, Najjar R P, Malkki H, Knoblauch K, Dumortier D, Gronfier C, Cooper HM. (2012) An inexpensive Arduino-based LED stimulator system for vision research. Journal of Neuroscience Methods 211, 227–236 download
Teikari P, Najjar RP, Malkki H, Knoblauch K, Dumortier D, Cornut PL, Denis P, Cooper HM, Gronfier C (2012) Refined flicker photometry technique to measure ocular lens density. Journal of the Optical Society of America A, 29, 2469–2478 download
Challet E, Dumont S, Mehdi MK, Allemann C, Bousser T, Gourmelen S, Sage-Ciocca D, Hicks D, Pévet P, Claustrat B (2012) Aging-like circadian disturbances in folate-deficient mice. Neurobiol Aging, 34(6):1589-98
Champier J, Claustrat F, Nazaret N, Fèvre Montange M, Claustrat B (2012) Folate depletion changes gene expression of fatty acid metabolism, DNA synthesis, and circadian cycle in male mice. Nutr Res, 32:124-32
Chang AM, Santhi N, St Hilaire M, Gronfier C, Bradstreet DS, Duffy JF, Lockley SW, Kronauer RE, Czeisler CA (2012) Human responses to bright light of different durations. J Physiol, 590 (Pt 13):3103-12
Daneault V, Vandewalle G, Hébert M, Teikari P, Mure LS, Doyon J, Gronfier C, Cooper HM, Dumont M, Carrier J (2012) Does pupil constriction under blue and green monochromatic light exposure change with age? J Biol Rhythms, 27(3):257-64.
Klerman H, St Hilaire MA, Kronauer RE, Gooley JJ, Gronfier C, Hull JT, Lockley SW, Santhi N, Wang W, Klerman EB (2012) Analysis method and experimental conditions affect computed circadian phase from melatonin data. PLoS One, 7(4):e33836
Duffy JF, Cain SW, Chang AM, Phillips AJK, Münch MY, Gronﬁer C, Wyatt JK, Dijk DJ, Wright Jr KP, Czeisler CA (2011) Sex difference in the near-24-hour intrinsic period of the human circadian timing system doi: 10.1073/pnas.1010666108 download
Vezoli J, Fifel K, Leviel V, Dehay C, Kennedy H, Cooper HM, Gronfier C, Procyk E (2011) Early Presymptomatic and Long-Term Changes of Rest Activity Cycles and Cognitive Behavior in a MPTP-Monkey Model of Parkinson’s Disease. PLoS One, 2011, 6(8):e23952 download
Ahowesso C, Li XM, Zampera S, Peteri-Brunbäck B, Dulong S, Beau J, Hossard V, Filipski E, Delaunay F, Claustrat B, Lévi F (2011) Sex and dosing-time dependencies in irinotecan-induced circadian disruption. Chronobiol Int, 28:458-70
Danilenko KV, Plisov IL, Cooper HM, Wirz-Justice A, Hébert M (2011) Human cone light sensitivity and melatonin rhythms following 24-h continuous illumination Chronobiol Int, Vol. 28 (5) 407-414
Guénolé F, Godbout R, Nicolas A, Franco P, Claustrat B, Baleyte JM (2011) Melatonin for disordered sleep in individuals with autism spectrum disorders: systematic review and discussion. Sleep Med Rev 15: 379-387
Quera-Salva MA, Hartley S, Claustrat B, Brugieres L (2011) Circadian rhythm disturbances associated with psychiatric symptoms in a patient with a pineal region tumor Am J Psychiatry, 168: 99-100
Taillard J, Philip P, Claustrat B, Capelli A, Coste O, Chaumet G, Sagaspe P (2011) Time course of neurobehavioral alertness during extended wakefulness in morning- and evening-type healthy sleepers. Chronobiol Int, 28:520-7
Mnie Fiali O, Faure C, Lambas-Senas L, El Mansari M, Belblidia H, Gondard E, Etievant A, Scarna H, Didier A, Berod A, Blier P, Haddjeri N (2011) Pharmacological blockade of 5-HT7 receptors induces a fast antidepressant-like response. Neuropsychopharmacology. 36(6):1275-88.
Renard E,Palombi K, Gronfier C, Pepin JL, Neol C, Chiquet C, Romanet JP (2010) 24-hour (nyctohemeral) rhythm of intraocular pressure and ocular perfusion pressure in normal tension glaucoma patients. IOVS 51(2):882-9
Dollet A, Albrecht U, Cooper HM, Dkhissi-Benyahya O. (2010) Cones are required for normal temporal responses to light of phase shifts and clock gene expression. Chronobiology International 27(4): 768-81 download
Pina G, Brun J, Tissot S, Claustrat B (2010) Long-term alteration of daily melatonin, 6-sulfatoxymelatonin, cortisol ad temperarure profiles in burn patients: a preliminary report Chronobiology International, 27(2): 378-392 download
Leston J, Harthe C, Brun J, Mottolese C, Mertens P, Sindou M, Claustrat B (2010) Melatonin is released in the third ventricle in humans. A study in movement disorders. Neurosci Lett, 469: 294-297
Moussaouiti R, Bouhaddou N, Sabbar M, Cooper HM, Lakhdar-Ghazal N (2010) Phase and Period Responses of the Jerboa Jaculus orientalis to Short Light Pulses. Chronobiol Int, 27(7):1348-1364
Oosthuizen MK, Bennett NC, Cooper HM (2010) Photic induction of Fos in the SCN of African mole-rats: responses to increasing irradiance. Chronobiol Int, 27(8): 1532–1545
Ravassard P, Pachoud B, Comte JC, Mejia-Perez C, ScotÈ-Blachon C, Gay N, Claustrat B, Touret M, Luppi PH, Salin PA (2009) Paradoxical (REM) sleep deprivation causes a large and rapidly reversible decrease in long-term potentiation, synaptic transmission, glutamate receptor protein levels, and ERK/MAPK activation in the dorsal hippocampus. Sleep, 32(2):227-40. download
Mure LS, Cornut PL, Rieux C, Drouyer E, Gronfier C, Denis P, Cooper HM (2009) Melanopsin bistabiliy: A fly’s eye technology in the human retina. PloS One, 4(6):e5991
Cooper HM, Mure LS (2008) Expected and unexpected properties of melanopsin signalling. J Biol Rhythms 23(5): 392-93 download
Hut RA, Oklejewicz M, Rieux C, Cooper HM. (2008) Photic sensitivity ranges of hamster pupillary and circadian phase responses do not overlap. J Biol Rhythms 23: 37-48. download
Drouyer E, Rieux C, Hut RA, Cooper HM (2007) Responses of SCN neurons to light and dark adaptation: relative contributions of melanopsin and rod-cone inputs. J Neurosci 27(36): 9623-31. download
Dkhissi-Benyahya O, Gronfier C, De Vanssay W, Flamant F, Cooper HM (2007) Modeling the role of mid-wavelength cones in circadian responses to light. Neuron 53(5):677-87. download
Gronfier C, Wright KP Jr, Kronauer RE, Czeisler CA (2007) Entrainment of the human circadian pacemaker to longer-than-24-h days. Proc Natl Acad Sci U S A, 104(21):9081-6 download
Mure LS, Rieux C, Hattar S, Cooper HM. (2007) Melanopsin-dependent nonvisual responses: evidence for photopigment bistability in vivo J Biol Rhythms 22(5): 411-24 download
Canaple L, Rambaud J, Dkhissi-Benyahya O, Rayet B, Tan NS, Michalik L, Delaunay F, Wahli W, Laudet V (2006) Reciprocal regulation of BMAL1 and PPARa defines a novel positive feedback loop in the murine liver circadian clock. Mol Endocrinol 20(8):1715-27 download
Dkhissi-Benyahya O, Rieux C, Hut RA, Cooper HM. (2006) Immunohistochemical evidence for a melanopsin cone in human retina. IOVS, 47(4):1636-41. download
Serrano A., Haddjeri N., Lacaille J-C., Robitaille R. (2006) Network interactions between GABA interneurons and glial cells in hippocampal heterosynaptic depression. J Neurosci. 26(20): 5370-5380.
El Mansari M., Sanchez C, Chouvet G., Renaud B. and Haddjeri N. (2005) Effects of acute and long-term administration of escitalopram and citalopram on serotonin neurotransmission: an in vivo electrophysiological study in rat brain. Neuropsychopharmacology, 30(7): 1269-1277.
Gronfier C, Wright KP, Jewett ME, Kronauer RE, Czeisler CA (2004) Efficacy of a single sequence of intermittent bright light pulses for delaying circadian phase in humans. Am J Physiol Endocrinol Metab, 287:E174-E181. download
Haddjeri N., Lavoie N., Blier P. (2004) Noradrenergic modulation of raphe 5-HT neuronal firing and hippocampal 5-HT release in vivo in the rat brain. Neuropsychopharmacology. Neuropsychopharmacology. 29(10):1800-1806.
Glickman G, Hanifin J, Rollag MD, Wang J, Cooper HM, Brainard GC. (2003) Inferior retinal light exposure is more effective than superior retinal exposure in suppressing melatonins in humans J. Biol Rhythms, 18(1):71-79. download
Chiquet C, Dkhissi-Benyahya O, Szel A, Degrip WJ, Cooper HM (2002) Characterisation of calbindin positive cones in four primate species. Neuroscience. 115(4):1323-33. download
Rieux C, Carney R, Lupi D, Dkhissi-Benyahya O, Janssen K, Cooper HM. (2002) Analysis of immunohistochemical label of Fos protein in the suprachiasmatic nucleus: comparison of different methods of quantification. J. Biol. Rhythms. 17(2): 121-136. download
Haddjeri N., Blier P. (2001) Sustained blockade of NK1 receptors enhances serotonin neurotransmission. Biological Psychiatry. 53(3): 191-199.
Brandenberger G, Gronfier C, Chapotot F, Simon C, Piquard F (2000) Effect of sleep deprivation on overall 24h growth hormone secretion Lancet suppl download
Dkhissi-Benyahya O, Sicard B, Cooper HM (2000) Effects of irradiance and stimulus duration on early gene expression (Fos) in the suprachiasmatic nucleus : temporal summation and reciprocity. J Neurosci 20(20):7790-7. download
Haddjeri N., Szabo S.T., de Montigny C., Blier P. (2000) Increased tonic activation of rat forebrain 5-HT1A receptors by lithium addition to antidepressant treatments. Neuropsychopharmacology. 22(4): 346-356
Haddjeri N., de Montigny C., Blier P. (1999) Modulation of the firing activity of dorsal raphe 5-HT neurons and locus coeruleus NA neurons by (±)pindolol Biological Psychiatry. 45(9): 1163-1169.