The French National Centre for Scientific Research

Circadian clock, sleep and homeostatic plasticity in mood disorders

Team leader : Tsvetan Serchov

Mood disorders are among the most commonly diagnosed disabling mental diseases. Despite the numerous pathophysiological hypotheses, elucidating the neurobiological basis of depression remains one of the foremost challenges in modern psychiatry.

Disruptions of sleep and circadian rhythm are associated with the development of various psychiatric diseases. Chronotherapies, which include a variety of strategies that modulate biological clock and sleep-wake cycle, such as sleep deprivation and light therapy, are alternative treatments for mood and sleep disorders. We have recently shown that the rapid antidepressant effects of acute sleep deprivation depend on enhanced adenosinergic and glutamatergic signaling. However, the involvement of the circadian clock in the antidepressant action of different chronotherapies and the pathophysiology of mood disorders is not yet well understood.

Using a combination of molecular biological methods, in vivo electrophysiology and complex behavioural analyses, we aim:

  1. To investigate the role of the circadian clock in the pathophysiology and treatment of depression
  2. To characterize the crosstalk between circadian and sleep homeostatic mechanisms on glutamatergic signaling in the rapid antidepressant therapy
  3. To study the impact of adenosinergic signaling mediating the effects of sleep loss on mood.


Principal investigator; Researcher

Tsvetan Serchov

Wilf Gardner
PhD student

David Sarrazin
Research Engineer

Carole Marchese
Master M2 student, Neuroscience

Martin Balzinger

Prof. Dr. Claus Normann (Psychiatry, Uniklinik Freiburg)
Prof. Dr. Volker A. Coenen (Neurozentrum, Uniklinik Freiburg)
Prof. Dr. Bernd Fakler (Physiology, University Freiburg)

Methodological approaches:

Genetically modified mouse models
Quantitative PCR, SDS-PAGE, Western blotting, Immunohystochemistry
Classical behavioral tests and complex automatic behavioral modeling and analyses via IntelliCage
In Vivo Electrophysiology: LFP and EEG (sleep) recordings


Fondation pour la Recherche Medical (FRM)
University of Strasbourg Institute for Advanced Studies (USIAS)
German Research Foundation (DFG)

Selected publications

Vestring S, Serchov T*, Normann C.J (2021) Animal Models of Depression – Chronic Despair Model (CDM). Vis Exp. (175). doi: 10.3791/62579. PMID: 34633373.

van Calker D, Serchov T*. (2021) The “Missing Heritability”-Problem in Psychiatry: Is the interaction of Genetics, Epigenetics and Transposable Elements a potential solution? Neurosci Biobehav Rev. S0149-7634 (21) 00134-2. doi: 10.1016/j.neubiorev. 2021.03.019.

Casarotto PC, Girych M, Fred SM, Kovaleva V, Moliner R, Enkavi G, Biojone C, Cannarozzo C, Sahu MP, Kaurinkoski K, Brunello CA, Steinzeig A, Winkel F, Patil S, Vestring S, Serchov T, Diniz CRAF, Laukkanen L, Cardon I, Antila H, Rog T, Piepponen TP, Bramham CR, Normann C, Lauri SE, Saarma M, Vattulainen I, Castrén E. (2021) Antidepressant drugs act by directly binding to TRKB neurotrophin receptors. Cell. 184(5):1299-1313.e19. doi: 10.1016/j.cell.2021.01.034.

Sun L, Verkaik-Schakel RK, Biber K, Plösch T, Serchov T* (2021) Antidepressant treatment is associated with epigenetic alterations of Homer1 promoter in a mouse model of chronic depression J Affect Disord. 279:501-509, doi: 10.1016/j.jad.2020.10.040.

Serchov T*, Schwarz I, Theiss A, Sun L, Holz A, Döbrössy MD, Schwarz MK, Normann C, Biber K, van Calker D. (2019) Enhanced adenosine A1 receptor and Homer1a expression in hippocampus modulates the resilience to stress-induced depression-like behavior. Neuropharmacology. 107834. doi: 10.1016/j.neuropharm.2019.

Holz A, Mülsch F, Schwarz MK, Hollmann M, Döbrössy MD, Coenen VA, Bartos M, Normann C, Biber K, van Calker D, Serchov T*. (2019) Enhanced mGlu5 Signaling in Excitatory Neurons Promotes Rapid Antidepressant Effects via AMPA Receptor Activation. Neuron. pii: S0896-6273(19)30637-3. doi: 10.1016/j.neuron.2019.07.011.

van Calker D, Biber K, Domschke K, Serchov T*. (2019) The Role of Adenosine Receptors in Mood and Anxiety Disorders. J Neurochem. doi: 10.1111/jnc.14841.

Serchov T, Clement HW, Schwarz MK, Iasevoli F, Tosh DK, Idzko M, Jacobson KA, de Bartolomeis A, Normann C, Biber K, van Calker D. (2015) Increased Signaling via Adenosine A1 Receptors, Sleep Deprivation, Imipramine, and Ketamine Inhibit Depressive-like Behavior via Induction of Homer1a. Neuron. 87(3):549-62. doi: 10.1016/j.neuron.2015.07.010.


The French National Centre for Scientific Research